Obesity and meningioma: a US population-based study paired with analysis of a multi-institutional cohort.

OBJECTIVE: Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort. METHODS: National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS. RESULTS: From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043). CONCLUSIONS: Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

Modular Phoneme Processing in Human Superior Temporal Gyrus.

Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

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.

Remyelination protects neurons from DLK-mediated neurodegeneration.

Chronic demyelination is theorized to contribute to neurodegeneration and drive progressive disability in demyelinating diseases like multiple sclerosis. Here, we describe two genetic mouse models of inducible demyelination, one distinguished by effective remyelination, and the other by remyelination failure and persistent demyelination. By comparing these two models, we find that remyelination protects neurons from apoptosis, improves conduction, and promotes functional recovery. Chronic demyelination of neurons leads to activation of the mitogen-associated protein kinase (MAPK) stress pathway downstream of dual leucine zipper kinase (DLK), which ultimately induces the phosphorylation of c-Jun in the nucleus. Both pharmacological inhibition and CRISPR/Cas9-mediated disruption of DLK block c-Jun phosphorylation and the apoptosis of demyelinated neurons. These findings provide direct experimental evidence that remyelination is neuroprotective and identify DLK inhibition as a potential therapeutic strategy to protect chronically demyelinated neurons.

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.

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.

Percutaneous CT-guided trigeminal tractotomy-nucleotomy under general anesthesia for intractable craniofacial pain.

OBJECTIVE: When used to treat craniofacial pain, CT-guided trigeminal tractotomy-nucleotomy (TR-NC) is usually performed with local anesthesia. Unfortunately, local anesthesia is insufficient for patients with such severe pain that they cannot tolerate the required head positioning while awake. This study aimed to contextualize previous findings associated with TR-NC performed under general anesthesia. The authors examined clinical and operative factors that could impact postoperative pain outcomes. METHODS: This is a retrospective single-institution cohort study of patients who underwent a percutaneous CT-guided TR-NC under general anesthesia at a single institution between 2012 and 2019. Outcome data were analyzed. RESULTS: Twenty-five patients underwent CT-guided TR-NC procedures under general anesthesia; 23 met the inclusion criteria and underwent a total of 31 procedures. The procedure success rate was 74% (23/31). Approximately 50% and 40% of procedures provided pain relief for at least 6 and 12 months, respectively. The median duration of pain relief was 153 days. Adverse events, all minor and transient, occurred following 6/31 (19%) of procedures. Patients with a body mass index > 25 were less likely to experience a successful TR-NC (p = 0.045). Higher electrode ablation temperatures (p = 0.033) and more medial entry trajectories relative to the midsagittal plane (p = 0.029) characterized successful procedures. CONCLUSIONS: These results suggest that CT-guided TR-NC performed under general anesthesia is safe and effective. Postoperative outcomes were found to be associated with a number of clinical and operative factors. Such associations should be further explored and evaluated in the context of future, better-powered analyses.

Constructing 2D maps of human spinal cord activity and isolating the functional midline with high-density microelectrode arrays.

Intraoperative neuromonitoring (IONM) is a widely used practice in spine surgery for early detection and minimization of neurological injury. IONM is most commonly conducted by indirectly recording motor and somatosensory evoked potentials from either muscles or the scalp, which requires large-amplitude electrical stimulation and provides limited spatiotemporal information. IONM may inform of inadvertent events during neurosurgery after they occur, but it does not guide safe surgical procedures when the anatomy of the diseased spinal cord is distorted. To overcome these limitations and to increase our understanding of human spinal cord neurophysiology, we applied a microelectrode array with hundreds of channels to the exposed spinal cord during surgery and resolved spatiotemporal dynamics with high definition. We used this method to construct two-dimensional maps of responsive channels and define with submillimeter precision the electrophysiological midline of the spinal cord. The high sensitivity of our microelectrode array allowed us to record both epidural and subdural responses at stimulation currents that are well below those used clinically and to resolve postoperative evoked potentials when IONM could not. Together, these advances highlight the potential of our microelectrode arrays to capture previously unexplored spinal cord neural activity and its spatiotemporal dynamics at high resolution, offering better electrophysiological markers that can transform IONM.

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.

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.

Speech-related auditory salience detection in the posterior superior temporal region.

Processing auditory human speech requires both detection (early and transient) and analysis (sustained). We analyzed high gamma (70-110 Hz) activity of intracranial electroencephalography waveforms acquired during an auditory task that paired forward speech, reverse speech, and signal correlated noise. We identified widespread superior temporal sites with sustained activity responding only to forward and reverse speech regardless of paired order. More localized superior temporal auditory onset sites responded to all stimulus types when presented first in a pair and responded in recurrent fashion to the second paired stimulus in select conditions even in the absence of interstimulus silence; a novel finding. Auditory onset activity to a second paired sound recurred according to relative salience, with evidence of partial suppression during linguistic processing. We propose that temporal lobe auditory onset sites facilitate a salience detector function with hysteresis of 200 ms and are influenced by cortico-cortical feedback loops involving linguistic processing and articulation.

Changing Hands: A Rising Role of the Tumor Surgeon in Teaching Sylvian Fissure Dissection.

OBJECTIVE: The landscape of microneurosurgery has changed considerably over the past 2 decades, with a decline in indications for open surgery on cerebrovascular pathology and ever-increasing indications for open resection of brain tumors. This study investigated how these trends in case volume affected residents' training experiences in microsurgery and, specifically, Sylvian fissure dissection. METHODS: Resident case logs were reviewed, identifying open cerebrovascular operations and craniotomies for tumor. Operations involving Sylvian fissure dissection were identified through operative reports. Changes in case number by resident were plotted over time, and linear regression was applied. RESULTS: Among 23 chief residents, 3045 operations were identified, 1071 of which were for cerebrovascular pathology and 1974 for tumor. Open cerebrovascular experience decreased (P < 0.0001) while tumor volume remained unchanged (P = 0.221). The number of Sylvian fissure dissections per resident did not change over time overall (P = 0.583) or within cerebrovascular operations (P = 0.071). The number of Sylvian fissure dissections in tumor operations increased (P = 0.004). This effect was predominated by an increase in intraaxial tumors approached via Sylvian fissure dissection (P = 0.003). The proportion of Sylvian fissure dissections in tumor surgery increased from 15% in 2009 to 34% by 2019 (P = 0.003). CONCLUSIONS: Residents are seeing an increasing proportion of their Sylvian fissure dissection experience during tumor operations. The distribution of this experience will continue to evolve as surgical indications change but suggests a growing role for tumor surgeons in resident training in microsurgery.

Dural Arteriovenous Fistula Presenting as Trigeminal Neuralgia: 2 Case Reports and Review of the Literature.

BACKGROUND: Dural arteriovenous fistulae (dAVFs) can sporadically compress the root entry zone of the trigeminal nerve or the Gasserian ganglion and therefore be a rare cause of isolated or complicated trigeminal neuralgia (TN). CASE DESCRIPTION: We describe 2 cases of TN related to dAVF treated similarly with transarterial embolization but with divergent outcomes. Further, we completed a comprehensive literature review of previously reported cases to date. A sparse but growing literature with regards to this specific and rare but salient cause of TN was noted. The type of dAVF most commonly found to cause TN was that of a tentorial nidus, a lesion generally accepted to be at high risk of hemorrhage and in need of urgent treatment. This warrants imaging for new TN presentations to ensure that a dangerous lesion does not represent the underlying cause, especially when the TN symptoms are comorbid with other symptoms such as a bruit. Treatments pursued span the range of open surgery, endovascular treatment, and radiosurgery with great success in treating both the TN symptoms, as well as the rupture risk of the dAVF itself in most cases. Indeed, endovascular approaches are becoming more widely employed for these cases over time, often resolving the abnormality on first treatment attempt. Other cases reach resolution after employing a combination of treatment modalities. CONCLUSIONS: This work highlights that dAVFs, particularly the tentorial type, are capable of causing TN symptomatically identical to that of other etiologies and that treatment of the dAVF itself is often sufficient.