Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Impact of white matter networks on risk for memory decline following resection versus ablation in temporal lobe epilepsy.

BACKGROUND: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries. METHODS: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)). RESULTS: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01). CONCLUSIONS: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.

Flexible, scalable, high channel count stereo-electrode for recording in the human brain.

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.

Acoustic and language-specific sources for phonemic abstraction from speech.

Spoken language comprehension requires abstraction of linguistic information from speech, but the interaction between auditory and linguistic processing of speech remains poorly understood. Here, we investigate the nature of this abstraction using neural responses recorded intracranially while participants listened to conversational English speech. Capitalizing on multiple, language-specific patterns where phonological and acoustic information diverge, we demonstrate the causal efficacy of the phoneme as a unit of analysis and dissociate the unique contributions of phonemic and spectrographic information to neural responses. Quantitive higher-order response models also reveal that unique contributions of phonological information are carried in the covariance structure of the stimulus-response relationship. This suggests that linguistic abstraction is shaped by neurobiological mechanisms that involve integration across multiple spectro-temporal features and prior phonological information. These results link speech acoustics to phonology and morphosyntax, substantiating predictions about abstractness in linguistic theory and providing evidence for the acoustic features that support that abstraction.

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.

A cost analysis of MR-guided laser interstitial thermal therapy for adult refractory epilepsy.

OBJECTIVE: MR-guided laser interstitial thermal therapy (LITT) is used increasingly for refractory epilepsy. The goal of this investigation is to directly compare cost and short-term adverse outcomes for adult refractory epilepsy treated with temporal lobectomy and LITT, as well as to identify risk factors for increased costs and adverse outcomes. METHODS: The National Inpatient Sample (NIS) was queried for patients who received LITT between 2012 and 2019. Patients with adult refractory epilepsy were identified. Multivariable mixed-effects models were used to analyze predictors of cost, length of stay (LOS), and complications. RESULTS: LITT was associated with reduced LOS and overall cost relative to temporal lobectomy, with a statistical trend toward lower incidence of postoperative complications. High-volume surgical epilepsy centers had lower LOS overall. Longer LOS was a significant driver of increased cost for LITT, and higher comorbidity was associated with non-routine discharge. SIGNIFICANCE: LITT is an affordable alternative to temporal lobectomy for adult refractory epilepsy with an insignificant reduction in inpatient complications. Patients may benefit from expanded access to this treatment modality for both its reduced LOS and lower cost.

Preoperative white matter network organization and memory decline after epilepsy surgery.

OBJECTIVE: Risk for memory decline is a common concern for individuals with temporal lobe epilepsy (TLE) undergoing surgery. Global and local network abnormalities are well documented in TLE. However, it is less known whether network abnormalities predict postsurgical memory decline. The authors examined the role of preoperative global and local white matter network organization and risk of postoperative memory decline in TLE. METHODS: One hundred one individuals with TLE (n = 51 with left TLE and 50 with right TLE) underwent preoperative T1-weighted MRI, diffusion MRI, and neuropsychological memory testing in a prospective longitudinal study. Fifty-six age- and sex-matched controls completed the same protocol. Forty-four patients (22 with left TLE and 22 with right TLE) subsequently underwent temporal lobe surgery and postoperative memory testing. Preoperative structural connectomes were generated via diffusion tractography and analyzed using measures of global and local (i.e., medial temporal lobe [MTL]) network organization. Global metrics measured network integration and specialization. The local metric was calculated as an asymmetry of the mean local efficiency between the ipsilateral and contralateral MTLs (i.e., MTL network asymmetry). RESULTS: Higher preoperative global network integration and specialization were associated with higher preoperative verbal memory function in patients with left TLE. Higher preoperative global network integration and specialization, as well as greater leftward MTL network asymmetry, predicted greater postoperative verbal memory decline for patients with left TLE. No significant effects were observed in right TLE. Accounting for preoperative memory score and hippocampal volume asymmetry, MTL network asymmetry uniquely explained 25%-33% of the variance in verbal memory decline for left TLE and outperformed hippocampal volume asymmetry and global network metrics. MTL network asymmetry alone produced good diagnostic classification of memory decline in left TLE (i.e., an area under the receiver operating characteristic curve of 0.80-0.84 and correct classification of 65%-76% of cases with cross-validation). CONCLUSIONS: These preliminary data suggest that global white matter network disruption contributes to verbal memory impairment preoperatively and predicts postsurgical verbal memory outcomes in left TLE. However, a leftward asymmetry of MTL white matter network organization may confer the highest risk for verbal memory decline. Although this requires replication in a larger sample, the authors demonstrate the importance of characterizing preoperative local white matter network properties within the to-be-operated hemisphere and the reserve capacity of the contralateral MTL network, which may eventually be useful in presurgical planning.

White matter network organization predicts memory decline after epilepsy surgery.

The authors have withdrawn their manuscript owing to a substantial change in data analysis and findings/conclusions. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Investigating Deep Brain Stimulation of the Habenula: A Review of Clinical Studies.

OBJECTIVES: The aim of this study was to examine the current scientific literature on deep brain stimulation (DBS) targeting the habenula for the treatment of neuropsychiatric disorders including schizophrenia, major depressive disorder, and obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: Two authors performed independent data base searches using the PubMed, Cochrane, PsycINFO, and Web of Science search engines. The data bases were searched for the query ("deep brain stimulation" and "habenula"). The inclusion criteria involved screening for human clinical trials written in English and published from 2007 to 2020. From the eligible studies, data were collected on the mean age, sex, number of patients included, and disorder treated. Patient outcomes of each study were summarized. RESULTS: The search yielded six studies, which included 11 patients in the final analysis. Treated conditions included refractory depression, bipolar disorder, OCD, schizophrenia, and major depressive disorder. Patients with bipolar disorder unmedicated for at least two months had smaller habenula volumes than healthy controls. High-frequency stimulation of the lateral habenula attenuated the rise of serotonin in the dorsal raphe nucleus for treating depression. Bilateral habenula DBS and patient OCD symptoms were reduced and maintained at one-year follow up. Low- and high-frequency stimulation DBS can simulate input paths to the lateral habenula to treat addiction, including cocaine addiction. More data are needed to draw conclusions as to the impact of DBS for schizophrenia and obesity. CONCLUSIONS: The habenula is a novel target that could aid in reducing neuropsychiatric symptoms and should be considered in circuit-specific investigation of neuromodulation for psychiatric disorders. More information needs to be gathered and assessed before this treatment is fully approved for treatment of neuropsychiatric conditions.

Psychiatric outcomes after temporal lobe surgery in patients with temporal lobe epilepsy and comorbid psychiatric illness: A systematic review and meta-analysis.

BACKGROUND: The currently available evidence is unclear in regard to psychiatric outcomes of temporal lobe epilepsy (TLE) in patients with comorbid psychiatric disorders (PD). AIM: To identify and synthesize psychiatric outcomes in patients with TLE and comorbid psychiatric illnesses before and after TLE surgery. METHODS: Studies were included if participants were adults and/or children with temporal epilepsy and comorbid psychiatric illness. Surgical interventions included focal resection (e.g., lobectomy, selective amygdalohippocampectomy) or stereotactic laser ablation. Included studies reported on pre- and post- surgery data of comorbid psychiatric illness (e.g., mood and anxiety disorders, depression, psychosis, adjustment disorders, non-epileptic seizures, and personality disorders). RESULTS: Ten studies were included in the review. The proportion of patients achieving PD resolution or improvements after surgery varied widely between studies, ranging from 15 % to 57 % at the reported follow-up time. Three studies reported on PD symptom worsening after surgery, with considerable variations of patient proportions across studies. Meta-analysis suggests that 43 % of patients demonstrated improvement and 33 % of patients showed a worsening in psychiatric scores across all studies. Preliminary data from three studies suggest that seizure control may be associated with favourable psychiatric outcomes. CONCLUSION: A considerable proportion of reported TLE patients with comorbid psychiatric illnesses have improvement in their psychiatric symptoms after temporal lobe epilepsy surgery. There is scarcity of detailed outcome reporting including symptom scores, and to date, predictive factors for favourable vs unfavourable outcomes in this patient population are not clear. Further research on the topic is warranted.

Widespread ripples synchronize human cortical activity during sleep, waking, and memory recall.

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such "binding" of different components of mental events into unified representations occurs is unknown. The "binding-by-synchrony" theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ("ripples") occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memory retrieval and perhaps generally in cognition.

Mindfulness Meditation in the Treatment of Chronic Pain.

Chronic pain is a leading cause of disability in the United States. Limited efficacy associated with pharmacologic management and surgical interventions in refractory patients has led to further exploration of cognitive and behavioral interventions as both an adjunctive and primary therapeutic modality. Mindfulness-based meditation has shown to be effective in reducing pain in randomized studies of chronic pain patients as well as models of experimentally induced pain in healthy participants. These studies have revealed specific neural mechanisms which may explain both short-term and sustained pain relief associated with mindfulness-based interventions.

Gender Equality in Neurosurgery and Strategic Goals Toward a More Balanced Workforce.

The Women in Neurosurgery (WINS) and the American Association of Neurological Surgeons published a white paper in 2008 setting an ambitious goal for women to comprise 20% of neurosurgery residents by 2012 and 20% of practicing neurosurgeons by 2020. Although there has been steady progress, we have fallen short of these benchmarks. We take this opportunity to look back at the accomplishments made over the past decade and provide an update on our present status. We evaluate current barriers toward progress and propose new goals, highlighting the systemic changes necessary to accomplish them. We propose the following updated recommendations to recruit and retain diverse talent into the neurosurgical workforce. (1) Neurosurgical departments and societies should provide diverse, early formal mentorship opportunities for medical students, residents, and junior faculty members. (2) Parental leave policies must be delineated, promoted, and enforced for all neurosurgeons, with greater awareness of internal discrimination and normalization of the discussion surrounding this topic. (3) We need to strive for compensation equity, with transparency in compensation mechanisms and regular assessment of compensation metrics. (4) Departments and institutions must have a zero-tolerance policy for sexual harassment and discrimination and establish a safe reporting structure. Finally, we propose attainable benchmarks toward achieving gender balance in the neurosurgical workforce, with a goal for women to comprise 30% of the entering residency class by 2030 and to comprise 30% of practicing neurosurgeons by 2038. We hope that this will guide further progress toward our future of building a balanced workforce.

The importance of basal-temporal white matter to pre- and post-surgical naming ability in temporal lobe epilepsy.

OBJECTIVE: Emerging research highlights the importance of basal-temporal cortex, centered on the fusiform gyrus, to both pre-surgical naming ability and post-surgical naming outcomes in temporal lobe epilepsy (TLE). In this study, we investigate whether integrity of the white matter network that interconnects this basal region to the distributed language network affects naming ability and risk for post-surgical naming decline. METHODS: Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-surgical dataset included 50 healthy controls, 47 left TLE (L-TLE), and 41 right TLE (R-TLE) patients. All participants completed pre-surgical T1- and diffusion-weighted MRI (dMRI), as well as neuropsychological tests of auditory and visual naming. Nineteen L-TLE and 18 R-TLE patients underwent anterior temporal lobectomy (ATL) and also completed post-surgical neuropsychological testing. Pre-surgical fractional anisotropy (FA) of the white matter directly beneath the fusiform neocortex (i.e., superficial white matter; SWM) and of deep white matter tracts with connections to the basal-temporal cortex [inferior longitudinal fasciculus (ILF) and inferior frontal occipital fasciculus (IFOF)] was calculated. Clinical variables, hippocampal volume, and FA of each white matter tract or region were examined in linear regressions with naming scores, or change in naming scores, as the primary outcomes. RESULTS: Pre-surgically, higher FA in the bilateral ILF, bilateral IFOF, and left fusiform SWM was associated with better visual and auditory naming scores (all ps < 0.05 with FDR correction). In L-TLE, higher pre-surgical FA was also associated with less naming decline post-surgically, but results varied across tracts. When including only patients with typical language dominance, only integrity of the right fusiform SWM was associated with less visual naming decline (p = .0018). DISCUSSION: Although a broad network of white matter network matter may contribute to naming ability pre-surgically, the reserve capacity of the contralateral (right) fusiform SWM may be important for mitigating visual naming decline following ATL in L-TLE. This shows that the study of the structural network interconnecting the basal-temporal region to the wider language network has implications for understanding both pre- and post-surgical naming in TLE.

Association Between Microstructural Asymmetry of Temporal Lobe White Matter and Memory Decline After Anterior Temporal Lobectomy.

BACKGROUND AND OBJECTIVES: Risk for memory decline is a substantial concern in patients with temporal lobe epilepsy (TLE) undergoing anterior temporal lobectomy (ATL). Although prior studies have identified associations between memory and integrity of white matter (WM) networks within the medial temporal lobe (MTL) preoperatively, we contribute a study examining whether microstructural asymmetry of deep and superficial WM networks within the MTL predicts postoperative memory decline. METHODS: Patients with drug-resistant TLE were recruited from 2 epilepsy centers in a prospective longitudinal study. All patients completed preoperative T1 and diffusion-weighted MRI (DWI) as well as preoperative and postoperative neuropsychological testing. Preoperative fractional anisotropy (FA) of the WM directly beneath the neocortex (i.e., superficial WM [SWM]) and of deep WM tracts associated with memory were calculated. Asymmetry was calculated for hippocampal volume and FA of each WM tract or region and examined in linear and logistic regressions with preoperative to postoperative memory change as the primary outcome. RESULTS: Data were analyzed from 42 patients with TLE (19 left TLE [LTLE], 23 right TLE [RTLE]) who underwent ATL. Leftward FA asymmetry of the entorhinal SWM was associated with decline on prose and associative recall in LTLE, whereas leftward FA asymmetry of the uncinate fasciculus (UNC) was associated with decline on prose recall only. After controlling for preoperative memory score and hippocampal volume, leftward FA asymmetry of the entorhinal SWM uniquely contributed to decline in both prose and associative recall (ß = -0.46; SE 0.14 and ß = -0.68; SE 0.22, respectively) and leftward FA asymmetry of the UNC uniquely contributed to decline in prose recall (ß = -0.31; SE 0.14). A model combining asymmetry of hippocampal volume and entorhinal FA correctly classified memory outcomes in 79% of patients with LTLE for prose (area under the curve [AUC] 0.89; sensitivity 82%; specificity 75%) and 81% of patients for associative (AUC 0.79; sensitivity 83%; specificity 80%) recall. Entorhinal SWM asymmetry was the strongest predictor in both models. DISCUSSION: Preoperative asymmetry of deep WM and SWM integrity within the MTL is a strong predictor of postoperative memory decline in TLE, suggesting that surgical decision-making may benefit from considering each patient's WM network adequacy and reserve in addition to hippocampal integrity. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that preoperative asymmetry of deep WM and SWM integrity within the MTL is a predictor of postoperative memory decline.

Human brain mapping with multithousand-channel PtNRGrids resolves spatiotemporal dynamics.

Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 µm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.

Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN. METHODS: The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III). RESULTS: A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up. CONCLUSIONS: The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

Enhancing Safety in Epilepsy Surgery (EASINESS): Study Protocol for a Retrospective, Multicenter, Open Registry.

Introduction: Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy. Design: The Enhancing Safety in Epilepsy Surgery (EASINESS) study is a retrospectively conducted, multicenter, open registry. All patients undergoing mesial temporal lobe epilepsy surgery in participating centers between January 2015 and December 2019 are included in this study. The patient characteristics, preoperative diagnostic tools, surgical data, postoperative complications, and long-term seizure outcomes are recorded. Outcomes: The collected data will be used for establishing standardized reference values ("benchmarks") for this type of surgical procedure. The primary endpoints include seizure outcomes according to the International League Against Epilepsy (ILAE) classification and defined postoperative complications. Discussion: The EASINESS will define robust and standardized outcome references after amygdalohippocampectomy for temporal lobe epilepsy. After the successful definition of benchmarks from an international cohort of renowned centers, these data will serve as reference values for the evaluation of novel surgical techniques and comparisons among centers for future clinical trials. Clinical trial registration: This study is indexed at clinicaltrials.gov (NT 04952298).

Neurosurgical Treatments for Cancer Pain.

Cancer-related pain is a uniquely challenging entity for treating practitioners for a variety of reasons, including its often severe and medically refractory nature, the emotional and social circumstances surrounding the disease process, and the frequently associated limited life expectancy.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.