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Introduction: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy effectively treats medication-resistant essential tremor (ET). Usually, intracranial calcifications are excluded as no-pass zones because of their low penetrability which may limit the effectiveness of treatment and lead to unintended side effects. This case report illustrates the efficacy of unilateral MRgFUS for tremor control in a patient with extensive basal ganglia calcifications due to Fahr's disease., Case Presentation: A 69-year-old right-handed male with debilitating Fahn-Tolosa-Marin grade 3-4 bilateral hand tremor underwent unilateral left MRgFUS thalamotomy. The treatment involved careful preoperative planning to accommodate his extensive basal ganglia calcifications, element path consideration, and skull density ratio to ensure accurate and effective lesioning. Posttreatment, the patient exhibited complete abolition of tremor on the treated side with minor transient dysarthria and imbalance. Follow-up at 12 weeks posttreatment showed sustained tremor relief and an absence of any adverse effects, validating the procedural adjustments made to accommodate the unique challenges posed by his intracranial calcifications., Conclusion: MRgFUS can be safely and effectively applied in certain patients with extensive basal ganglia calcifications - in this case, due to Fahr's disease. This case report suggests expanding the application of MRgFUS to patients with extensive intracranial calcifications who previously might not have been considered suitable candidates for MRgFUS., (© 2024 S. Karger AG, Basel.)

Introduction: Patients considering therapeutic epilepsy surgery often seek to decrease the number of anti-seizure medications (ASMs) they need. Predicting such reductions remains challenging. Although predictors of seizure freedom after epilepsy surgery are well-established, long-term outcomes remain modest and factors associated with ASM reduction, even in the absence of seizure freedom, may improve surgical planning to align with patient goals., Methods: We studied a large multi-institutional cohort of patients who underwent epilepsy surgery between 2001 and 2022, with a minimum of two years follow-up. Preoperative features, including duration of epilepsy, epilepsy etiology, non-invasive investigation data, and total number of ASMs prescribed immediately prior to surgery were extracted for each patient. Primary endpoints included likelihood of ASM reduction and ASM freedom at multiple post-operative time points up to 15 years and stratified by seizure control., Results: A total of 250 patients were followed for a median of 6.0 (range 2, 22) years after intracranial EEG (iEEG) surgery. Significant ASM reduction was only observed in those who underwent subsequent resection, whereas those undergoing neuromodulation saw their ASM usage maintained. Engel I outcomes were the strongest driver of ASM reduction. In patients with persistent seizures, patients with lateralized seizure onset zones (SOZs) also achieved sustained ASM reduction over time. Similarly, an increased number of preoperative ASMs also corresponded to a higher likelihood of ASM reduction across all follow-up periods. Other preoperative factors, including seizure etiology, did not independently influence ASM reduction., Conclusions: Even patients with persistent seizures after epilepsy surgery can observe meaningful ASM reduction during long-term follow-up. ASM reduction may be a relevant secondary outcome measure for epilepsy surgery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Imbalance is the most commonly reported side effect following focused ultrasound (FUS) thalamotomy for essential tremor (ET). It remains unknown which patients are more likely to develop imbalance following FUS treatment., Objective: To identify preoperative and treatment-related sonication parameters that are predictive of imbalance following FUS treatment., Methods: We retrospectively collected demographic data, preoperative Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM) scores and FUS treatment parameters in patients undergoing FUS thalamotomy for treatment of ET. The presence of imbalance was evaluated at several discrete time-points with up to 4 years of follow-up. Multiple machine learning classifiers were built and evaluated, aiming to maximize accuracy while minimizing feature set., Results: Of the 297 patients identified, the presence of imbalance peaked at 1 week following operation at 79%. This declined rapidly with 29% reporting imbalance at 3 months, and only 15% at 4 years. At 1 week, total preoperative FTM scores and Maximum Energy delivered in FUS could predict the presence of imbalance at 92.8% accuracy. At 3 months, the total preoperative FTM scores and maximum power delivered could predict the presence of imbalance with 90.6% accuracy. Post-operative lesion size and extent into thalamic nuclei, internal capsule, and subthalamic regions were identified as likely key underlying drivers of these predictors., Conclusions: A machine learning model based on preoperative tremor scores and maximum energy/power delivered predicted the development of short-term imbalance and long-term imbalance following FUS thalamotomy., (© 2024 International Parkinson and Movement Disorder Society.)

Although three-dimensional (3D) genome architecture is crucial for gene regulation, its role in disease remains elusive. We traced the evolution and malignant transformation of colorectal cancer (CRC) by generating high-resolution chromatin conformation maps of 33 colon samples spanning different stages of early neoplastic growth in persons with familial adenomatous polyposis (FAP). Our analysis revealed a substantial progressive loss of genome-wide cis-regulatory connectivity at early malignancy stages, correlating with nonlinear gene regulation effects. Genes with high promoter-enhancer (P-E) connectivity in unaffected mucosa were not linked to elevated baseline expression but tended to be upregulated in advanced stages. Inhibiting highly connected promoters preferentially represses gene expression in CRC cells compared to normal colonic epithelial cells. Our results suggest a two-phase model whereby neoplastic transformation reduces P-E connectivity from a redundant state to a rate-limiting one for transcriptional levels, highlighting the intricate interplay between 3D genome architecture and gene regulation during early CRC progression., Competing Interests: Competing interests: G.K., A.J., D.L. and Z.S. are employees and shareholders of Ultima Genomics. M.P.S is a cofounder and scientific advisor of Personalis, Qbio, SensOmics, January AI, Mirvie, Protos, NiMo and Onza and is on the advisory board of Genapsys. E.D.E. is an employee and stockholder of Invitae and an advisor and stockholder of Taproot Health and Exir Bio. W.J.G. has affiliations with Guardant Health (consultant and scientific advisory board), Protillion Biosciences (Scientifica cofounder) and 10x and has licensed patents associated with ATAC-seq. All other authors declare no competing interests., (© 2024. The Author(s).)

Disorders of consciousness (DoC) are states of impaired arousal or awareness. Deep brain stimulation (DBS) is a potential treatment, but outcomes vary, possibly due to differences in patient characteristics, electrode placement, or stimulation of specific brain networks. We studied 40 patients with DoC who underwent DBS targeting the thalamic centromedian-parafascicular complex. Better-preserved gray matter, especially in the striatum, correlated with consciousness improvement. Stimulation was most effective when electric fields extended into parafascicular and subparafascicular nuclei-ventral to the centromedian nucleus, near the midbrain-and when it engaged projection pathways of the ascending arousal network, including the hypothalamus, brainstem, and frontal lobe. Moreover, effective DBS sites were connected to networks similar to those underlying impaired consciousness due to generalized absence seizures and acquired lesions. These findings support the therapeutic potential of DBS for DoC, emphasizing the importance of precise targeting and revealing a broader link between effective DoC treatment and mechanisms underlying other conscciousness-impairing conditions., Competing Interests: COMPETING INTERESTS AELW, MR, HF, FLWVJS, JT, SBS, JL, MMJC, KB, MUF, RJ, JEI, PWC, DF, ADB, BLE, and DC have no competing interests to report. MDF has intellectual property on the use of brain connectivity imaging to analyze lesions and guide brain stimulation, has consulted for Magnus Medical, Soterix, Abbott, Boston Scientific, and Tal Medical, and has received research funding from Neuronetics. AH reports lecture fees for Boston Scientific and is a consultant for Neuromodulation and Abbott. JDR has received past consulting payments from Medtronic, Corlieve, ClearPoint, Medtronic, and NeuroPace, and currently consults for Turing Medical.

While ventricular shunts are the main treatment for adult hydrocephalus, shunt malfunction remains a common problem that can be challenging to diagnose. Computer vision-derived algorithms present a potential solution. We designed a feasibility study to see if such an algorithm could automatically predict ventriculomegaly indicative of shunt failure in a real-life adult hydrocephalus population. We retrospectively identified a consecutive series of adult shunted hydrocephalus patients over an eight-year period. Associated computed tomography scans were extracted and each scan was reviewed by two investigators. A machine learning algorithm was trained to identify the lateral and third ventricles, and then applied to test scans. Results were compared to human performance using Sørensen-Dice coefficients, calculated total ventricular volumes, and ventriculomegaly as documented in the electronic medical record. 5610 axial images from 191 patients were included for final analysis, with 52 segments (13.6% of total data) reserved for testing. Algorithmic performance on the test group averaged a Dice score of 0.809 ± 0.094. Calculated total ventricular volumes did not differ significantly between computer-derived volumes and volumes marked by either the first reviewer or second reviewer (p > 0.05). Algorithm detection of ventriculomegaly was correct in all test cases and this correlated with correct prediction of need for shunt revision in 92.3% of test cases. Though development challenges remain, it is feasible to create automated algorithms that detect ventriculomegaly in adult hydrocephalus shunt malfunction with high reliability and accuracy., (© 2024. The Author(s).)

Objective: Many patients pursue epilepsy surgery with the hope of reducing or stopping anti-seizure medications (ASMs), in addition to reducing their seizure frequency and severity. While ASM decrease is primarily driven by surgical outcomes and patient preferences, preoperative estimates of meaningful ASM reduction or discontinuation are uncertain, especially when accounting for the various forking paths possible following intracranial EEG (iEEG), including resection, neuromodulation, or even the absence of further surgery. Here, we characterize in detail the ASM reduction in a large cohort of patients who underwent iEEG, facilitating proactive, early counseling for a complicated cohort considering surgical treatment., Methods: We identified a multi-institutional cohort of patients who underwent iEEG between 2001 and 2022, with a minimum of two years follow-up. The total number of ASMs prescribed immediately prior to surgery, choice of investigation modality, and subsequent surgical treatment were extracted for each patient. Primary endpoints included decreases in ASM counts from preoperative baseline to various follow-up intervals., Results: A total of 284 patients were followed for a median of 6.0 (range 2,22) years after iEEG surgery. Patients undergoing resection saw an average reduction of ∼ 0.5 ASMs. Patients undergoing neuromodulation saw no decrease and trended towards requiring increased ASM usage during long-term follow-up. Only patients undergoing resection were likely to completely discontinue all ASMs, with an increasing probability over time approaching ∼ 10 %. Up to half of resection patients saw ASM decreases, which was largely stable during long-term follow-up, whereas only a quarter of neuromodulation patients saw a reduction, though their ASM reduction decreased over time., Conclusions: With the increasing use of stereotactic EEG and non-curative neuromodulation procedures, realistic estimates of ASM reduction and discontinuation should be considered preoperatively. Almost half of patients undergoing resective surgery can expect to reduce their ASMs, though only a tenth can expect to discontinue ASMs completely. If reduction is not seen early, it likely does not occur later during long-term follow-up. Less than a third of patients undergoing neuromodulation can expect ASM reduction, and instead most may require increased usage during long-term follow-up., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. D. Rolston has received consulting payments from Medtronic, Corlieve, and NeuroPace. J.D. Rolston is supported in part by an NIH /NINDS career development award (K23 NS114178). S. Tobochnik is supported in part by a VA Career Development Award (V1CDA2022–68) and has received research support from Eisai. All other authors have no disclosures to report., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Patients with medication-resistant disabling epilepsy should be considered for potential epilepsy surgery. If noninvasive techniques are unable to identify the location of the seizure onset zone (SOZ), it becomes necessary to consider intracranial investigations. Stereo-electroencephalography (SEEG) is currently the preferred method for such monitoring, however foramen ovale (FO) electrodes offer a less invasive alternative that may be suitable in certain situations. Previous studies have demonstrated the effectiveness of FO electrodes in suspected mesial temporal epilepsy, nevertheless, increased experience with FO electrode use could further enhance their safety and efficacy. Therefore, we conducted an analysis of recent FO electrode investigations to assess their utility in surgical decision making, post resection outcomes, and complication rates., Methods: We conducted a retrospective analysis of 61 patients who underwent FO placement at Mass General Brigham between 2009 and 2020. Patient and seizure characteristics, preoperative investigation data, and seizures outcomes were collected. In addition, identified predictors of FO utility using logistic regression., Results: A total of 61 patients were identified. FO evaluation localized the SOZ in 56 % of patients. Complications were encountered in 1.6 % of patients. Subsequent surgical resection was pursued by 49 % of patients, with 56 % becoming seizure free, and 67 % having favorable seizure outcomes at last follow-up. Multivariate analysis identified younger patients with a higher number of preoperative ASMs as more likely to undergo subsequent treatment, however, these features were not predictive features of SOZ localization, seizure freedom, or favorable seizure outcomes. In patients with bitemporal or cross-over onsets on scalp EEG, FO was able to identify the SOZ in 79 %, whereas in patients with discordant or unclear onset, the rates were 71 % and 45 %, respectively., Conclusion: In a contemporary cohort, FO electrode placement had a low complication rate and a high utility primarily in cases of unclear laterality of mesial temporal onsets or discordance between scalp EEG and other pre-FO investigation data in cases of suspected mesial temporal onsets., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Essential tremor (ET) is the most common movement disorder globally and has negative impacts on quality of life. While medical treatments exist, approximately 50% of patients have tremor that is refractory to medication or experience intolerable medication side effects. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an option for these patients and while incisionless, it is still invasive, although less so than other surgical treatments such as deep brain stimulation and radiofrequency thalamotomy. Despite MRgFUS being FDA-approved since 2016, there is still no current consensus on the best approaches for targeting, imaging, and outcome measurement. A 2-day workshop held by the Focused Ultrasound Foundation in September of 2023 convened experts and critical stakeholders in the field to share their knowledge and experiences. The goals of the workshop were to determine the optimal target location within the thalamus and compare best practices for localizing the target and tracking patient outcomes. This paper summarizes the current landscape, important questions, and discussions that will help direct future treatments to improve patient care and outcomes.

Objective: Numerous studies have examined epilepsy surgery outcomes, yet the variability in the level of detail reported hampers our ability to apply these findings broadly across patient groups. Established reporting standards in other clinical research fields enhance the quality and generalizability of results, ensuring that the insights gained from studying these surgeries can benefit future patients effectively. This study aims to assess current reporting standards for epilepsy surgery research and identify potential gaps and areas for enhancement., Methods: The Enhancing the Quality and Transparency of Health Research (EQUATOR) repository was accessed from inception to April 27, 2023, yielding 561 available reporting standards. Reporting standards were manually reviewed in duplicate independently for applicability to epilepsy and/or neurosurgery research. The reporting standards had to cover the following aspects in human studies: (1) reporting standards for epilepsy/epilepsy surgery and (2) reporting standards for neurosurgery. Disagreements were resolved by a third author. The top five neurosurgery, neurology, and medicine journals were also identified through Google Scholar's citation index and examined to determine the relevant reporting standards they recommended and whether those were registered with EQUATOR., Results: Of the 561 EQUATOR reporting standards, 181 were pertinent to epilepsy surgery. One was related to epilepsy, six were specific to surgical research, and nine were related to neurological/neurosurgical research. The remaining 165 reporting standards were applicable to research across various disciplines and included but were not limited to CONSORT (Consolidated Standards of Reporting Trails), STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). None of these required reporting factors associated with epilepsy surgery outcomes, such as duration of epilepsy or magnetic resonance imaging findings., Significance: Reporting standards specific to epilepsy surgery are lacking, reflecting a gap in standards that may affect the quality of publications. Improving this gap with a set of specific reporting standards would ensure that epilepsy surgery studies are more transparent and rigorous in their design., (© 2024 International League Against Epilepsy.)

Objective: A third of the patients who undergo intracranial EEG (iEEG) for seizure-onset zone (SOZ) localization do not proceed to resective surgery for epilepsy, and over half of those who do continue to have seizures following treatment. To better identify candidates who are more likely to see benefits from undergoing iEEG, we investigated preoperative and iEEG peri-operative features associated with the localization of a putative SOZ, undergoing subsequent surgical treatment, and seizure outcomes., Methods: We conducted a retrospective cohort study of consecutive patients who underwent iEEG from 2001 to 2022 at two institutions. Outcomes included SOZ identification, proceeding to surgical treatment (resection vs. neuromodulation), and subsequent seizure freedom., Results: We identified 329 unique patients who were followed for a median of 3.9 (IQR:7) years, with a minimum of 2-year follow-up for seizure outcomes analyses. Multivariate analysis identified lateralized and lobar localization on scalp EEG (OR 3.8, p = 0.001) to be associated with SOZ localization. Patients with unilateral localization on scalp EEG (OR 3.0, p = 0.003), unilateral preimplantation hypothesis (OR 3.1, p = 0.001), and lesional preoperative MRI (OR 2.1, p = 0.033) were more likely to undergo resection than neuromodulation. Similarly, a unilateral pre-implantation hypothesis (OR 2.6, p < 0.001) favored seizure freedom, whereas prior neuromodulation (OR 0.3, p = 0.013) decreased the odds. Larger number of preoperative anti-seizure medications (ASMs) did not influence seizure freedom rates but did decrease favorable (Engel I, II) seizure outcomes (OR 0.7, p = 0.026)., Interpretation: Non-invasive localization data prior to iEEG are associated with subsequent resection and seizure freedom, independent of iEEG localization. Factors predictive of SOZ localization are not necessarily predictive of post-operative seizure freedom., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Status Epilepticus (SE), unresponsive to medical management, is associated with high morbidity and mortality. Surgical management is typically considered in these refractory cases. The best surgical approach for affected patients remains unclear; however, given the lack of controlled trials exploring the role of surgery. We performed a systematic review according to PRIMSA guidelines, including case reports and series describing surgical interventions for patients in SE. Cases (157 patients, median age 12.9 years) were followed for a median of 12 months. Patients were in SE for a median of 21 days before undergoing procedures including: focal resection (36.9%), functional hemispherectomy (21%), lobar resection (12.7%), vagus nerve stimulation (VNS) (12.7%), deep brain stimulation (DBS) (6.4%), multiple subpial transection (MST) (3.8%), responsive neurostimulation (RNS) (1.9%), and cortical stimulator placement (1.27%), with 24 patients undergoing multiple procedures. Multiple SE semiologies were identified. 47.8% of patients had focal seizures, and 65% of patients had focal structural abnormalities on MRI. SE persisted for 36.8 ± 47.7 days prior to surgical intervention. SE terminated following surgery in 81.5%, terminated with additional adjuncts in 10.2%, continued in 1.9%, and was not specified in 6.4% of patients. Long-term seizure outcomes were favorable, with the majority improved and 51% seizure-free. Eight patients passed away in follow-up, of which three were in SE. Seizures emerging from one hemisphere were both more likely to immediately terminate (OR 4.7) and lead to long-term seizure-free status (OR 3.9) compared to nonunilateral seizures. No other predictors, including seizure focality, SE duration, or choice of surgical procedure, were predictors of SE termination. Surgical treatment of SE can be effective in terminating SE and leading to sustained seizure freedom, with many different procedures showing efficacy if matched appropriately with SE semiology and etiology. PLAIN LANGUAGE SUMMARY: Patients with persistent seizures (Status Epilepticus) that do not stop following medications can be treated effectively with surgery. Here, we systematically review the entirety of existing literature on surgery for treating status epilepticus to better identify how and when surgery is used and what patients do after surgery., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: Skull density ratio (SDR) is the ratio between the mean Hounsfield units of marrow and cortical bone, impacting energy transmission through the skull. Low SDR has been used as an exclusion criterion in major trials of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET). However, some studies have suggested that patients with low SDR can safely undergo MRgFUS with favorable outcomes. In this case-matched study, we aim to compare the characteristics, sonication parameters, lesion sizes, and clinical outcomes of patients with low SDR vs. patients with high SDR who underwent unilateral MRgFUS thalamotomy for medication-refractory ET., Methods: Between March 2016 and April 2023, all patients ( n  = 270) who underwent unilateral MRgFUS thalamotomy for medication-refractory ET at a single institution were classified as low SDR (<0.40) and high SDR (≥0.40). All clinical and radiological data was prospectively collected and retrospectively analyzed using non-case-matched and 1:1 case-matched methodology., Results: Thirty-one patients had low SDR, and 239 patients had high SDR. Fifty-six patients (28 in each cohort) were included in 1:1 case-matched analysis. There were no significant differences in baseline characteristics between the two groups in both non-case-matched and 1:1 case-matched analyses. In both analyses, compared to patients with high SDR, patients with low SDR required a significantly higher maximum sonication power, energy, and duration, and reached a lower maximum temperature with smaller lesion volumes. In the non-case-matched and case-matched analyses, low SDR patients did not have significantly less tremor control at any postoperative timepoints. However, there was a higher chance of procedure failure in the low SDR group with three patients not obtaining an appropriately sized lesion. In both analyses, imbalance was observed more often in high SDR patients on postoperative day 1 and month 3., Discussion: ET patients with SDR <0.40 can be safely and effectively treated with MRgFUS, though there may be higher rates of treatment failure and intraoperative discomfort., Competing Interests: GC is a consultant for InSightec. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ng, Blitz, Chua and Cosgrove.)

Objective: Surgical intervention can be curative or palliative for drug-resistant focal epilepsy. However, if the seizure onset zone (SOZ) cannot be adequately localized via noninvasive tests, intracranial EEG (iEEG) recordings are often carried out to develop surgical plans in appropriate candidates. Stereotactic EEG (SEEG), subdural EEG (SDE), and SDE with depth electrodes (hybrid) are major tools used for investigation, but there is no class 1 or 2 evidence comparing the effectiveness of these modalities., Methods: The authors identified an institutional cohort of patients who underwent iEEG monitoring between 2001 and 2022. Demographic data, preoperative clinical features, iEEG intervention, and follow-up data were identified. Primary study endpoints included the following: 1) likelihood of SOZ localization; 2) likelihood of surgical treatment after iEEG; 3) seizure outcomes; and 4) complications., Results: A total of 329 patients were identified (176 in the SEEG, 60 in the SDE, and 93 in the hybrid cohort) who were followed for a median of 5.4 (IQR 6.8) years. Baseline characteristics, including demographics, mean age at epilepsy diagnosis, mean age at iEEG investigation, number of preoperative antiseizure medications, and preoperative seizure frequency, were not statistically different across the 3 cohorts. Patients in the SEEG cohort were more likely to have their SOZ localized than were the patients in the SDE group (OR 2.3) and were less likely to undergo subsequent resection (OR 0.3) or to have complications (OR 0.4), although there was no statistical difference with respect to likelihood of undergoing any subsequent neurosurgical treatment, or with respect to favorable seizure outcomes. Patients in the hybrid cohort were more likely to have SOZ localized than were patients in the SDE group (OR 3.1), but were more likely to undergo resection (OR 4.9) or any neurosurgical treatment (OR 2.5) compared to patients in the SEEG group. Patients in the hybrid cohort had better seizure outcomes compared to the SDE (OR 2.3) but not to the SEEG group., Conclusions: Patients in the SEEG group were more likely to have their SOZ localized and patients in the SDE group were more likely to undergo resection, but they did not differ with respect to seizure outcomes.

Current applications of neurostimulation for generalized epilepsy use a one-target-fits-all approach that is agnostic to the specific epilepsy syndrome and seizure type being treated. The authors describe similarities and differences between the 2 "archetypes" of generalized epilepsy-Lennox-Gastaut syndrome and Idiopathic Generalized Epilepsy-and review recent neuroimaging evidence for syndrome-specific brain networks underlying seizures. Implications for stimulation targeting and programming are discussed using 5 clinical questions: What epilepsy syndrome does the patient have? What brain networks are involved? What is the optimal stimulation target? What is the optimal stimulation paradigm? What is the plan for adjusting stimulation over time?, Competing Interests: Disclosure A.E.L. Warren, Steven Tobochnik, Melissa M.J. Chua, Hargunbir Singh, and Michaela A. Stamm have no disclosures to report. John D. Rolston has received consulting payments from Medtronic, Corlieve, and NeuroPace., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: Commercially available lead localization software for deep brain stimulation (DBS) often relies on postoperative computed tomography (CT) scans to define electrode positions. When cases are performed with intraoperative MRI, another imaging set exists with which to perform these localizations. To compare DBS localization error between postoperative CT scans and intraoperative MRI., Methods: A retrospective cohort of patients who underwent MRI-guided placement of DBS electrodes using the ClearPoint platform was identified. Using Brainlab Elements, postoperative CT scans were coregistered to intraoperative magnetic resonance images visualizing the ClearPoint guidance sheaths and ceramic stylets. DBS electrodes were identified in CT scans using Brainlab's lead localization tool. Trajectory and vector errors were quantified between scans for each lead in each patient., Results: Eighty patients with a total of 157 implanted DBS electrodes were included. We observed mean trajectory and vector errors of 0.78 ± 0.44 mm (range 0.1-2.0 mm) and 1.57 ± 0.79 mm (range 0.2-4.2 mm), respectively, between postoperative CT and intraoperative MRI. There were 7 patients with CT scans collected at multiple time points. Trajectory error increased by 0.15 ± 0.42 mm ( P = .31), and vector error increased by 0.22 ± 0.53 mm ( P = .13) in the later scans. Across all scans, there was no significant association between trajectory ( P = .053) or vector ( P = .98) error and the date of CT acquisition. DBS electrodes targeting the subthalamic nucleus had significantly greater trajectory errors ( P = .02) than those targeting the globus pallidus pars internus nucleus., Conclusion: Commercially available software produced largely concordant lead localizations when comparing intraoperative MRIs with postoperative CT scans, with trajectory errors on average <1 mm. CT scans tend to be more comparable with intraoperative MRI in the immediate postoperative period, with increased time intervals associated with a greater magnitude of error between modalities., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Introduction: Magnetic-resonance-guided focused ultrasound (MRgFUS) thalamotomy uses multiple converging high-energy ultrasonic beams to produce thermal lesions in the thalamus. Early postoperative MR imaging demonstrates the location and extent of the lesion, but there is no consensus on the utility or frequency of postoperative imaging. We aimed to evaluate the evolution of MRgFUS lesions and describe the incidence, predictors, and clinical effects of lesion persistence in a large patient cohort., Methods: A total of 215 unilateral MRgFUS thalamotomy procedures for essential tremor (ET) by a single surgeon were retrospectively analyzed. All patients had MR imaging 1 day postoperatively; 106 had imaging at 3 months and 32 had imaging at 1 year. Thin cut (2 mm) axial and coronal T2-weighted MRIs at these timepoints were analyzed visually on a binary scale for lesion presence and when visible, lesion volumes were measured. SWI and DWI sequences were also analyzed when available. Clinical outcomes including tremor scores and side effects were recorded at these same time points. We analyzed if patient characteristics (age, skull density ratio), preoperative tremor score, and sonication parameters influenced lesion evolution and if imaging characteristics correlated with clinical outcomes., Results: Visible lesions were present in all patients 1 day post- MRgFUS and measured 307.4 ± 128.7 mm 3 . At 3 months, residual lesions (excluding patients where lesions were not visible) were 83.6% smaller and detectable in only 54.7% of patients ( n = 58). At 1 year, residual lesions were detected in 50.0% of patients ( n = 16) and were 90.7% smaller than 24 h and 46.5% smaller than 3 months. Lesions were more frequently visible on SWI (100%, n = 17), DWI ( n = 38, 97.4%) and ADC ( n = 36, 92.3%). At 3 months, fewer treatment sonications, higher maximum power, and greater distance between individual sonications led to larger lesion volumes. Volume at 24 h did not predict if a lesion was visible later. Lesion visibility at 3 months predicted sensory side effects but was not correlated with tremor outcomes., Discussion: Overall, lesions are visible on T2-weighted MRI in about half of patients at both 3 months and 1 year post-MRgFUS thalamotomy. Certain sonication parameters significantly predicted persistent volume, but residual lesions did not correlate with tremor outcomes., Competing Interests: GC is a consultant for InSightec. JR was previously a consultant for ClearPoint. NM’s laboratory has received research support unrelated to the current study from InSightec. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Blitz, Chua, Ng, Segar, Jha, McDannold, DeSalvo, Rolston and Cosgrove.)

Objective: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking., Methods: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming., Results: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power., Significance: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording., (© 2023 International League Against Epilepsy.)

Background: Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice., Objectives: To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD., Methods: Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure., Results: Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year., Conclusions: MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Objectives: Compare the effects of ice slurry ingestion at low and normal doses on endurance capacity and exertional heat stress-induced gastrointestinal perturbations., Design: Randomised, cross-over design., Methods: Twelve physically active males completed four treadmill running trials, ingesting ice slurry (ICE) or ambient drink (AMB) at 2 g·kg -1 (Normal; N) or 1 g·kg -1 (Low; L) doses every 15-min during exercise and 8 g·kg -1 (N) or 4 g·kg -1 (L) pre- and post-exercise. Pre-, during and post-exercise serum intestinal fatty-acid binding protein ([I-FABP]) and lipopolysaccharide ([LPS]) concentrations were determined., Results: Pre-exercise gastrointestinal temperature (T gi ) was lower in L + ICE than L + AMB (p < 0.05), N + ICE than N + AMB (p < 0.001) and N + ICE than L + ICE (p < 0.001). Higher rate of T gi rise (p < 0.05) and lower estimated sweat rate (p < 0.001) were observed in N + ICE than N + AMB. Rate of T gi rise was similar at low dose (p = 0.113) despite a lower estimated sweat rate in L + ICE than L+AMB (p < 0.01). Time-to-exhaustion was longer in L + ICE than L + AMB (p < 0.05), but similar between N + ICE and N + AMB (p = 0.142) and L + ICE and N + ICE (p = 0.766). [I-FABP] and [LPS] were similar (p > 0.05)., Conclusions: L + ICE elicited a lower heat dissipation compensatory effect with similar endurance capacity as N + ICE. Ice slurry conferred no protection against exertional heat stress-induced gastrointestinal perturbations., Competing Interests: Declaration of interest statement None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is a rapidly developing technique used for tremor relief in tremor-predominant Parkinson's disease (PD) and essential tremor that has demonstrated successful results. Here, we describe the neuropathological findings in a woman who died from a fall 10 days after successful MRgFUS for tremor-predominant PD. Histological analysis demonstrates the characteristic early postoperative MRI findings including 3 distinct zones on T2-weighted imaging: (1) a hypointense core, (2) a hyperintense region with hypointense rim, and (3) a slightly hyperintense, poorly marginated surrounding area. Histopathological analyses also demonstrate the suspected cellular processes composing each of these regions including central hemorrhagic necrosis with surrounding cytotoxic edema and a rim of mostly unaffected vasogenic edema with some reactive and reparative processes. Overall, this case demonstrates the correlation of postoperative imaging findings with the subacute neuropathological findings after MRgFUS for PD., (© 2023 S. Karger AG, Basel.)

Introduction: Prompt dissemination of clinical trial results is essential for ensuring the safety and efficacy of intracranial neurostimulation treatments, including deep brain stimulation (DBS) and responsive neurostimulation (RNS). However, the frequency and completeness of results publication, and reasons for reporting delays, are unknown. Moreover, the patient populations, targeted anatomical locations, and stimulation parameters should be clearly reported for both reproducibility and to identify lacunae in trial design. Here, we examine DBS and RNS trials from 1997 to 2022, chart their characteristics, and examine rates and predictors of results reporting., Methods: Trials were identified using ClinicalTrials.gov. Associated publications were identified using ClinicalTrials.gov and PubMed.gov. Pearson's χ2 tests were used to assess differences in trial characteristics between published and unpublished trials., Results: Across 449 trials, representing a cumulative cohort of 42,769 patient interventions, there were 37 therapeutic indications and 44 stimulation targets. The most common indication and target were Parkinson's disease (40.55%) and the subthalamic nucleus (35.88%), respectively. Only 0.89% of trials were in pediatric patients (11.58% were mixed pediatric and adult). Explored targets represented 75% of potential basal ganglia targets but only 29% of potential thalamic targets. Allowing a 1-year grace period after trial completion, 34/169 (20.12%) had results reported on ClinicalTrials.gov, and 107/169 (63.31%) were published. ∼80% of published trials included details about stimulation parameters used. Published and unpublished trials did not significantly differ by trial characteristics., Conclusion: We highlight key knowledge and performance gaps in DBS and RNS trial research. Over one-third of trials remain unpublished &gt;1 year after completion; pediatric trials are scarce; most of the thalamus remains unexplored; about one-in-five trials fail to report stimulation parameters; and movement disorders comprise the most studied indications., (© 2023 S. Karger AG, Basel.)

Objective: Stereoelectroencephalography (SEEG) and MRI-guided laser interstitial thermal therapy (MRgLITT) have emerged as safe, effective, and less invasive alternatives to subdural grid placement and open resection, respectively, for the localization and treatment of medically refractory epilepsy (MRE) in children. Reported pediatric experience combining these complementary techniques is limited, with traditional workflows separating electrode removal and ablation/resection. The authors describe the largest reported series of pediatric epilepsy patients who underwent MRgLITT following SEEG contrasted with a cohort that underwent craniotomy following SEEG, combining ablation/resection with electrode explantation as standard practice., Methods: The medical records of all patients with MRE who had undergone SEEG followed by MRgLITT or open resection/disconnection at Boston Children's Hospital between November 2015 and December 2020 were retrospectively reviewed. Primary outcome variables included surgical complication rates, length of hospital stay following treatment, and Engel classification at the last follow-up., Results: Of 74 SEEG patients, 27 (median age 12.1 years, 63% female) underwent MRgLITT and 47 (median age 12.1 years, 49% female) underwent craniotomy. Seventy patients (95%) underwent SEEG followed by combined electrode removal and treatment. Eight MRgLITT cases (30%) and no open cases targeted the insula (p < 0.001). Complication rates did not differ, although trends toward more subdural/epidural hematomas, infarcts, and permanent unanticipated neurological deficits were evident following craniotomy, whereas a trend toward more temporary unanticipated neurological deficits was seen following MRgLITT. The median duration of hospitalization after treatment was 3 and 5 days for MRgLITT and open cases, respectively (p = 0.078). Seizure outcomes were similar between the cohorts, with 74% of MRgLITT and craniotomy patients attaining Engel class I or II outcomes (p = 0.386) at the last follow-up (median 1.1 and 1.9 years, respectively)., Conclusions: MRgLITT and open resection following SEEG can both effectively treat MRE in pediatric patients and generally can be performed in a two-surgery workflow during a single hospitalization. In appropriately selected patients, MRgLITT tended to be associated with shorter hospitalizations and fewer complications following treatment and may be best suited for focal deep-seated targets associated with relatively challenging open surgical approaches.

Traumatic brain injury is a complex and highly heterogeneous disease due to the host of concomitant injuries that may accompany the initial insult. Due to the dynamic interplay between the injuries that may arise, the management of these injuries is challenging. In a small subset of patients with traumatic brain injury, cerebral vascular injury may occur, which presents its own diagnostic and therapeutic challenges. These vascular injuries often present in a delayed fashion, thereby going unnoticed by clinicians. Early recognition and treatment of these injuries is crucial, given their high morbidity and mortality. Through a critical review of the literature, we present the spectrum of cerebrovascular injuries that may occur with traumatic brain injury and discuss classification systems that are used to stratify cerebrovascular injury. We then focus on the diagnosis of cerebral vascular injury using different neuroimaging modalities. Lastly, we explore the treatment of these injuries ranging from antiplatelet therapies to endovascular and open vascular procedures. By highlighting the pitfalls and challenges of this complex disease, we hope to provide clinicians with the framework to recognize and treat vascular injuries that are seen in patients with traumatic brain injury., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since the 1980s, there have been several reports for the use of intraoperative ultrasound as a useful adjunct in spinal surgery. However, with the advent of newer cutting-edge imaging modalities, the use of intraoperative ultrasound in spine surgery has largely fallen out of favor. Despite this, intraoperative ultrasound continues to provide several advantages over other intraoperative techniques such as magnetic resonance imaging and computed tomography including being more cost-effective, efficient, and easy to operate and interpret. Additionally, it remains the only method for the real-time visualization of soft tissue and pathologies. This paper focuses on the advantages of using intraoperative ultrasound, especially in cases of intradural lesions and lesions ventral to the thecal sac when approaching posteriorly.

Background: Ureteral fistulas are abnormal connections between the ureters and other organs. Maintaining a high index of suspicion is important because they can precipitate dangerous complications such as sepsis and renal failure. Connections to a vertebral body have only been documented in the setting of trauma. Here, we present a 67-year-old female with a ureterovertebral fistula extending into the L3 vertebral body., Case Description: A 67-year-old female with a history of endometrial adenocarcinoma underwent surgery and radiation therapy complicated by a right ureteral obstruction requiring stent placement. Five months later, she developed back pain and MR-documented L2-L4 level osteomyelitis/discitis with a psoas phlegmon/abscess, which required drainage. A fistula was later identified between the right ureter and the psoas phlegmon. Despite percutaneous nephrostomy placement and aggressive IV antibiotic treatment, she was readmitted for persistent signs of infection over the next few months during which time she was repeatedly and unsuccessfully treated with multiple antibiotics. Sixteen months following her original stent placement, she developed right leg weakness and urinary incontinence attributed to the MR-documented ureteropsoas fistula extending into the L3 vertebral body. Following a nephrectomy with ureteral ligation, an L3 anterior corpectomy with interbody fusion for discitis at both L2-L3 and L3-L4, and an L1-L5 posterolateral fusion, she was discharged to a rehabilitation center., Conclusion: In patients with recurrent sepsis, osteomyelitis/discitis, or psoas abscess of unknown origin or who have a significant history (e.g., pelvic malignancy, radiation, and instrumentation), it is important to consider urodynamic testing to look for a ureteral leak or fistula., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Background: Parsonage-Turner syndrome (PTS) is a rare brachial plexopathy characterized by self-limiting shoulder girdle and upper arm pain followed by the upper extremity weakness and sensory changes. While the etiology is not well-understood, the most common cause of PTS is thought to be postviral. There are at least nine reports, to the best of our knowledge, of PTS associated with COVID-19 infection and nine reports associated with COVID-19 vaccination., Case Description: Here, we present a case of PTS after COVID-19 vaccination in a 64-year-old male and a review of the current literature., Conclusion: PTS can occur post-COVID-19 vaccination and should be on the differential diagnosis when patient continues to experience shoulder pain and develops weakness or sensory changes in the extremity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Objective: Despite understanding the associated adverse outcomes, identifying hospitalized patients at risk for sepsis is challenging. The authors aimed to characterize the epidemiology and clinical risk of sepsis in patients who underwent vertebral fracture repair for traumatic spinal injury (TSI)., Methods: The authors conducted a retrospective cohort analysis of adults undergoing vertebral fracture repair during initial hospitalization after TSI who were registered in the National Trauma Data Bank from 2011 to 2014., Results: Of the 29,050 eligible patients undergoing vertebral fracture repair, 317 developed sepsis during initial hospitalization. Of these patients, most presented after a motor vehicle accident (63%) or fall (28%). Patients in whom sepsis developed had greater odds of being male (adjusted OR [aOR] 1.5, 95% CI 1.1-1.9), having diabetes mellitus (aOR 1.5, 95% CI 1.11-2.1), and being obese (aOR 1.9, 95% CI 1.4-2.5). Additionally, they had greater odds of presenting with moderate (aOR 2.7, 95% CI 1.8-4.2) or severe (aOR 3.9, 95% CI 2.9-5.2) Glasgow Coma Scale scores and of having concomitant abdominal injuries (aOR 1.9, 95% CI 1.5-2.5) but not cranial, thoracic, or lower-extremity injuries. Interestingly, cervical spine injury was significantly associated with developing sepsis (OR 1.4, 95% CI 1.1-1.8), but thoracic and lumbar spine injuries were not. Spinal cord injury (OR 1.9, 95% CI 1.5-2.5) was also associated with sepsis regardless of level. Patients with sepsis were hospitalized approximately 16 days longer. They had greater odds of being discharged to rehabilitative care or home with rehabilitative care (OR 2.4, 95% CI 1.8-3.2) and greater odds of death or discharge to hospice (OR 6.0, 95% CI 4.4-8.1)., Conclusions: Among patients undergoing vertebral fracture repair, those with cervical spine fractures, spinal cord injuries, preexisting comorbidities, and severe concomitant injuries are at highest risk for developing postoperative sepsis and experiencing adverse hospital disposition.

Objectives: Vasospasm is a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) that generally occurs 4-14 days post-hemorrhage. Based on American Heart Association guidelines, the current understanding is that hyponatremic episodes may lead to vasospasm. Therefore, we sought to determine the association between repeated serum sodium levels of aSAH patients and its relationship to radiographic vasospasm., Materials and Methods: A single-center retrospective analysis from 2007-2016 was conducted of aSAH patients. Daily serum sodium levels were recorded up to day 14 post-admission. Hyponatremia was defined as a serum sodium value of < 135 mEq/L. We evaluated the relationship to radiologic vasospasm, neurologic deterioration, functional status at discharge, and mortality. A repeated measures analysis using a mixed-effect regression model was performed to assess the interindividual relationship between serum sodium trends and outcomes., Results: A total of 271 aSAH patients were included. There were no significant differences in interindividual serum sodium values over time and occurrence of radiographic vasospasm, neurologic deterioration, functional, or mortality outcomes (p = .59, p = .42, p = .94, p = .99, respectively) using the mixed-effect regression model. However, overall mean serum sodium levels were significantly higher in patients who had neurologic deterioration, poor functional outcome (mRS 3-6), and mortality., Conclusions: Serum sodium level variations are not associated with subsequent development of cerebral vasospasm in aSAH patients. These findings indicate that serum sodium may not have an impact on vasospasm, and avoiding hypernatremia may provide a neurologic, functional and survival benefit., Competing Interests: Declarations of Competing Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

We describe a 74-year-old male with intractable essential tremor (ET) and hyperostosis calvariae diffusa who was unsuccessfully treated with magnetic resonance-guided focused ultrasound (MRgFUS). A computed tomography performed prior to the procedure demonstrated a skull density ratio (SDR) of 0.37 and tricortical hyperostosis calvariae diffusa. No lesion was evident on post-MRgFUS MRI, and no improvement in the patient's hand tremor was noted clinically. We systematically reviewed the literature to understand outcomes for those patients with hyperostosis who have undergone MRgFUS. A comprehensive literature search using the PubMed, Cochrane, and Google Scholar databases identified 3 ET patients with hyperostosis who failed treatment with MRgFUS. Clinical findings, skull characteristics, treatment parameters, and outcomes were summarized, demonstrating different patterns/degrees of bicortical hyperostosis and variable SDRs (i.e., from 0.38 to ≥0.45). Although we have successfully treated patients with bicortical hyperostosis frontalis interna (n = 50), tricortical hyperostosis calvariae diffusa appears to be a contraindication for MRgFUS despite acceptable SDRs., (© 2022 S. Karger AG, Basel.)

Objectives: Aneurysms associated with hemorrhagic moyamoya disease (MMD) are reported to stabilize or recede following revascularization., Case Report/results: A 29 year-old male with no past medical history presented obtunded with diffuse intraventricular hemorrhage and vascular imaging demonstrating bilateral MMD without any associated aneurysms. He underwent a delayed right-sided STA-MCA bypass and pial synangiosis, and was subsequently discharged on hospital day 24 with a modified Rankin Scale score (mRS) of 2. He returned eleven days later from a rehabilitation facility with recurrent IVH. A saccular 5 mm right P4 segment posterior cerebral artery aneurysm was seen on a diagnostic angiogram and embolized with Onyx glue., Conclusions: Distal posterior circulation artery aneurysmal rupture is a rare cause of hemorrhagic MMD. This case demonstrates the capacity of these aneurysms to re-rupture following revascularization and underscores the importance of treating the aneurysms directly., (Copyright © 2021. Published by Elsevier Inc.)

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society. Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ 2 -test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR). Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% ( p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60-2.89). Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Muthiah, Chua, Griva, Low, Lim, Ng, Hwang, Yap, Iyer, Bonney, Anantharaman, Huang, Tan, Lee, Kow and Tai.)

Objective: Venous thromboembolism (VTE) can cause significant morbidity and mortality in hospitalized patients, and may disproportionately occur in patients with limited mobility following spinal trauma. The authors aimed to characterize the epidemiology and clinical predictors of VTE in pediatric patients following traumatic spinal injuries (TSIs)., Methods: The authors conducted a retrospective cohort analysis of children who experienced TSI, including spinal fractures and spinal cord injuries, encoded within the National Trauma Data Bank from 2011 to 2014., Results: Of the 22,752 pediatric patients with TSI, 192 (0.8%) experienced VTE during initial hospitalization. Proportionally, more patients in the VTE group (77%) than in the non-VTE group (68%) presented following a motor vehicle accident. Patients developing VTE had greater odds of presenting with moderate (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI] 1.4-4.8) or severe Glasgow Coma Scale scores (aOR 4.3, 95% CI 3.0-6.1), epidural hematoma (aOR 2.8, 95% CI 1.4-5.7), and concomitant abdominal (aOR 2.4, 95% CI 1.8-3.3) and/or lower extremity (aOR 1.5, 95% CI 1.1-2.0) injuries. They also had greater odds of being obese (aOR 2.9, 95% CI 1.6-5.5). Neither cervical, thoracic, nor lumbar spine injuries were significantly associated with VTE. However, involvement of more than one spinal level was predictive of VTE (aOR 1.3, 95% CI 1.0-1.7). Spinal cord injury at any level was also significantly associated with developing VTE (aOR 2.5, 95% CI 1.8-3.5). Patients with VTE stayed in the hospital an adjusted average of 19 days longer than non-VTE patients. They also had greater odds of discharge to a rehabilitative facility or home with rehabilitative services (aOR 2.6, 95% CI 1.8-3.6)., Conclusions: VTE occurs in a low percentage of hospitalized pediatric patients with TSI. Injury severity is broadly associated with increased odds of developing VTE; specific risk factors include concomitant injuries such as cranial epidural hematoma, spinal cord injury, and lower extremity injury. Patients with VTE also require hospital-based and rehabilitative care at greater rates than other patients with TSI.

Background: Chondromas are benign cartilaginous tumors that are rarely seen in the brain., Observations: A 58-year-old woman had undergone routine brain imaging after a motor vehicle accident and was incidentally found to have a right falcine lesion. Contrast magnetic resonance imaging showed a mostly nonenhancing mass with discontinuous rim enhancement. She was taken to the operating room and pathology revealed a chondroma., Lessons: Falcine intracranial chondromas are rare and typically misdiagnosed as meningiomas. Chondromas should be in the differential for patients presenting with nonenhancing falcine lesions., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2021 The authors.)

Background: Operating room (OR) inefficiency drives up cost, decreases revenue, and leads to surgeon, staff, and patient dissatisfaction. Given a low mean first-case start rate in our tertiary academic medical center, we developed a process to improve first-case start rates in an effort to increase OR efficiency., Methods: A working group of the OR Executive Committee was constituted to develop and implement a multistep operational plan. This plan was predicated on a sensible staggered start framework, coordination of stakeholder responsibilities, a visual preoperative Stop/Go checklist tool, real-time measurement, and feedback., Results: Within 11 days of implementation, 95% of first-start OR cases were tracked to start on time. Throughout the observation period (May 2015-July 2016), the goal of a daily mean 80% on-time start rate was either met or exceeded., Conclusions: Implementation of an organized collaborative effort led to dramatic improvements in first OR case on-time rates. Such improvement in OR utilization may lead to an increase in staff and patient satisfaction and cost reduction.

Background: Pure arterial malformations (PAMs) are rare vascular anomalies that are commonly mistaken for other vascular malformations. Because of their purported benign natural history, PAMs are often conservatively managed. The authors report the case of a ruptured PAM leading to subarachnoid hemorrhage (SAH) with intraventricular extension that was treated endovascularly., Observations: A 38-year-old man presented with a 1-day history of headaches and nausea. A computed tomography scan demonstrated diffuse SAH with intraventricular extension, and angiography revealed a right posterior inferior cerebellar artery-associated PAM. The PAM was treated with endovascular Onyx embolization., Lessons: To the authors' knowledge, only 2 other cases of SAH associated with PAM have been reported. In those 2 cases, surgical clipping was pursued for definitive treatment. Here, the authors report the first case of a ruptured PAM treated using an endovascular approach, showing its feasibility as a treatment option particularly in patients in whom open surgery is too high a risk., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2021 The authors.)

Background: Alterations in normal coagulation and hemostasis are critical issues that require special attention in the neurosurgical patient. These disorders pose unique challenges in the management of these patients who often have concurrent acute ischemic and hemorrhagic injuries. Although neurosurgical intervention in such cases may be unavoidable and potentially life-saving, these patients should be closely observed after instrumentation., Case Description: A 57-year-old male with liver cirrhosis secondary to amyloid light-chain amyloidosis was admitted to the intensive care unit for the management of delayed hydrocephalus. An external ventricular drain (EVD) was placed for the treatment and monitoring of hydrocephalus. Five days after EVD placement, a head computed tomography scan revealed a tract hemorrhage. However, on repeated imaging, the size of the hemorrhage continued to increase despite aggressive blood pressure control and several doses of phytonadione. Extensive coagulopathy workup was remarkable for low factor VII levels. In that setting, recombinant activated factor VII was administered to normalize factor VII levels, and the tract hemorrhage stabilized., Conclusion: To the best of our knowledge, this is the first case of spontaneous hemorrhage after EVD placement in the setting of liver cirrhosis-associated factor VII deficiency. Our case highlights the importance of identifying coagulation disorders in neurosurgical patients at high risk for coagulopathy and closely monitoring them postoperatively., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Surgical Neurology International.)

Magnetic resonance imaging-guided laser-induced thermal therapy (MRgLITT) is a minimally invasive surgical approach increasingly employed for precise targeted ablation of epileptogenic brain foci. Recent reports have described corpus callosotomy using MRgLITT, though its application in more extensive functional disconnections has not been documented. Here, the authors detail its use in achieving a palliative hemispherotomy in a 5-year-old with medically refractory hemiclonic seizures following a hemispheric infarction, highlighting a novel use of this surgical technique. In this particular case, open craniotomy was deemed high risk given the multiple medical comorbidities including congenital cardiac disease and end-stage renal failure. MRgLITT was considered an alternative approach with a lower risk for periprocedural hemodynamic perturbations. The patient tolerated the procedure well, attaining an Engel class IB outcome at 16 months' follow-up. This suggests that MRgLITT may be an alternative approach to an open hemispherectomy, particularly in cases in which multiple comorbidities pose significant risks and preclude an open procedure.

Purpose: Soft tissue sarcoma (STS) of the sella is exceptionally rare. We conducted a case series, literature review, and nationwide analysis of primary and iatrogenic (radiation-associated) STS of the sella to define the clinical course of this entity., Methods: This study employed a multi-institutional retrospective case review, literature review, and nationwide analysis using the National Cancer Database (NCDB)., Results: We report five patients who were diagnosed at three institutions with malignant STS of the sella. All patients presented with symptoms related to mass effect in the sellar region. All tumors extended to the suprasellar space, with the majority displaying extension into the cavernous sinus. All patients underwent an operation via a transsphenoidal approach with a goal of maximal safe tumor resection in four patients and biopsy for 1 patient. Histopathologic evaluation demonstrated STS in all patients. Post-operative adjuvant radiotherapy and chemotherapy were given to 2 and 1 out of 4 patients with known post-operative clinical course, respectively. The 1-year and 5-year overall survival rates were 100% (5/5) and 25% (1/4). Twenty-two additional reports of primary, non-iatrogenic STS of the sella were identified in the literature. Including the three cases from our series, treatment included resection in all cases, and adjuvant radiotherapy and chemotherapy were utilized in 50% (12/24) and 17% (4/24) of cases, respectively. The national prevalence of malignant STS is estimated to be 0.01% among all pituitary and sellar tumors within the NCDB., Conclusions: We report the prevalence and survival rates of STS of the sella. Multimodal therapy, including maximal safe resection, chemotherapy, and radiotherapy are necessary to optimize outcomes for this uncommon pathology.

Introduction: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients' insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies., Methods: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014-2015., Results: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p > 0.05), 59% of Medicaid patients (OR 2.3, p < 0.001), and 49% of self-pay patients (OR 3.4, p < 0.001). Medicare (OR 1.5, p = 0.002) and Medicaid (OR 1.4, p = 0.035) were both associated with higher likelihood of 90-day readmission compared to private insurance. In comparison, 30-day analyses did not unveil this discrepancy between Medicaid and privately insured, highlighting the merit for longer-term outcomes analyses in value-based care. Patients readmitted within 30 days versus those with later readmissions possessed different characteristics., Conclusions: Compared to patients with private insurance coverage, Medicaid and self-pay patients were significantly more likely to undergo non-elective resection of benign meningioma. Medicaid and Medicare insurance were associated with a higher likelihood of 90-day readmission; only Medicare was significant at 30 days. Both 30 and 90-day outcomes merit consideration given differences in readmitted populations.

Intraventricular melanoma is a very rare and highly malignant disease. Safe resection is the mainstay of treatment, but no standard guidelines exist for adjuvant therapy. Early histologic and molecular diagnosis is key for improved survival., Competing Interests: JDB has positions/equity in CITC Ltd. and Avidea Technologies and is a member of the board of scientific advisors for POCKiT Diagnostics. All other authors declare that they have no competing conflicts of interest., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: There is an increasing incidence of elderly patients requiring emergency laparotomy. Our study compares the outcomes of elderly patients undergoing emergency laparotomy against the outcomes of non-elderly patients., Methodology: Patients who underwent emergency laparotomy between 2015 and 2017 from the National University Hospital, Singapore, were included. Apart from demographic data, indication of surgery and surgical procedure performed were collected. Prospectively collected nutritional scores were evaluated. Outcome measures included duration of surgery, length of ICU and total hospital stay, post-operative complications, and mortality indices. We performed multivariate Cox regression analysis to determine the contribution of various risk factors towards overall survival following emergency laparotomy., Results: A total of 170 emergency laparotomies were performed. Compared to non-elderly patients, elderly patients had a significantly longer mean stay in hospital (31.5 vs. 18.6 days, p = 0.006) and mean stay in ICU (13.1 vs. 5.3 days, p = 0.003). More elderly patients suffered from post-laparotomy complications compared with non-elderly patients (65.8% vs. 37.4%, p < 0.001). 30-day mortality (31.5% vs. 8.8%, p = 0.019) and 1-year mortality (27.9% vs. 14.3%, p = 0.023) were higher in elderly patients compared with non-elderly patients. Interestingly, there was no statistically significant difference between elderly and non-elderly groups in both the global 3-MinNS as well as the global SGA nutritional scores. ASA status (HR 2.61, 95% CI 1.05-6.45, p = 0.038) was an independent risk factor for decreased survival following emergency laparotomy. Notably, while age ≥ 65 demonstrated a significant correlation with survival on univariate analysis (HR 1.03 (1.01-1.05), p = 0.003), this effect was lost following multivariate regression (HR 1.01 (0.453-2.23), p = 0.989)., Conclusion: Elderly patients suffer worse morbidity and mortality following emergency laparotomy. This is likely contributed by comorbidities resulting in higher ASA status.

Background: Acute left ventricular (LV) systolic failure as a consequence of acute severe brain injury with status epilepticus in a young infant is not common; managing such a patient on extracorporeal membrane oxygenation (ECMO), which requires proper anticoagulation adds further substrate to a particularly intriguing and novel case worthy of reporting. Takotsubo syndrome and its peculiar clinical presentation is not commonly reported in the paediatric population, yet the high likelihood of this diagnosis joining the dots up for this case invites our curiosity and reflection through the clinical management of this case., Case Presentation: A previously healthy 9-month-old local Chinese boy presented with generalised seizures secondary to acute severe brain injury, with signs of sympathetic overdrive, followed by rapidly progressive cardiogenic shock and respiratory failure, eventually requiring ECMO support. Neuroimaging at presentation revealed bilateral subdural haemorrhages. His cardiac function recovered within the next 24 h revealing the reversibility nature of Takotsubo cardiomyopathy., Conclusions: This is a captivating case depicting a series of unfortunate and unpredictable clinical events occurring in a previously well infant, which at initial presentation challenged the managing team with regards to its exact aetiology of acute brain injury and acute cardiorespiratory failure. Consideration of various differential diagnoses and finally narrowing down to that of stress-induced reversible cardiomyopathy (Takotsubo syndrome) following his intracranial bleed, versus that of coexisting dual pathology - acute brain injury with concomitant acute viral myocarditis, deepened our understanding of the pathophysiology of each disease process, and how it possibly interlinks between different organ systems.

Objective: Nonroutine discharge after elective spine surgery increases healthcare costs, negatively impacts patient satisfaction, and exposes patients to additional hospital-acquired complications. Therefore, prediction of nonroutine discharge in this population may improve clinical management. The authors previously developed a machine learning algorithm from national data that predicts risk of nonhome discharge for patients undergoing surgery for lumbar disc disorders. In this paper the authors externally validate their algorithm in an independent institutional population of neurosurgical spine patients., Methods: Medical records from elective inpatient surgery for lumbar disc herniation or degeneration in the Transitional Care Program at Brigham and Women's Hospital (2013-2015) were retrospectively reviewed. Variables included age, sex, BMI, American Society of Anesthesiologists (ASA) class, preoperative functional status, number of fusion levels, comorbidities, preoperative laboratory values, and discharge disposition. Nonroutine discharge was defined as postoperative discharge to any setting other than home. The discrimination (c-statistic), calibration, and positive and negative predictive values (PPVs and NPVs) of the algorithm were assessed in the institutional sample., Results: Overall, 144 patients underwent elective inpatient surgery for lumbar disc disorders with a nonroutine discharge rate of 6.9% (n = 10). The median patient age was 50 years and 45.1% of patients were female. Most patients were ASA class II (66.0%), had 1 or 2 levels fused (80.6%), and had no diabetes (91.7%). The median hematocrit level was 41.2%. The neural network algorithm generalized well to the institutional data, with a c-statistic (area under the receiver operating characteristic curve) of 0.89, calibration slope of 1.09, and calibration intercept of -0.08. At a threshold of 0.25, the PPV was 0.50 and the NPV was 0.97., Conclusions: This institutional external validation of a previously developed machine learning algorithm suggests a reliable method for identifying patients with lumbar disc disorder at risk for nonroutine discharge. Performance in the institutional cohort was comparable to performance in the derivation cohort and represents an improved predictive value over clinician intuition. This finding substantiates initial use of this algorithm in clinical practice. This tool may be used by multidisciplinary teams of case managers and spine surgeons to strategically invest additional time and resources into postoperative plans for this population.

Flow diverters are new generation stents that have recently garnered a large amount of interest for use in treatment of intracranial aneurysms. Flow diverters reduce blood flow into the aneurysm, with redirection along the path of the parent vessel. Flow stagnation into the aneurysm and neck coverage with subsequent endothelialization are the important synergistic mechanisms by which the therapy acts. Several studies have examined the mechanisms by which flow diverters subsequently lead to aneurysm occlusion. This review aims to provide a general overview of the flow diverters and their mechanism of action and potential implications. ANN NEUROL 2019;85:793-800., (© 2019 American Neurological Association.)

Oncolytic virotherapy (OVT) is a promising approach in which WT or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. In the last two decades, different oncolytic viruses (OVs) have been modified and tested in a number of preclinical studies, some of which have led to clinical trials in cancer patients. These clinical trials have revealed several critical limitations with regard to viral delivery, spread, resistance, and antiviral immunity. Here, we focus on promising research strategies that have been developed to overcome the aforementioned obstacles. Such strategies include engineering OVs to target a broad spectrum of tumor cells while evading the immune system, developing unique delivery mechanisms, combining other immunotherapeutic agents with OVT, and using clinically translatable mouse tumor models to potentially translate OVT more readily into clinical settings.

Objective: Literature review comparing post-tonsillectomy hemorrhage in pediatric and adult patients with and without suturing tonsil pillars to investigate whether suturing tonsil pillars reduces the risk of post-tonsillectomy hemorrhage., Review Methods: Online journal databases were searched using the key phrases "post tonsillectomy hemorrhage", "post tonsillectomy bleed", and "tonsil pillar suture". 10 published studies were found regarding tonsil pillar suturing, four directly related to postoperative bleeding and five focusing on postoperative pain reduction. There was one study that evaluated both pain and bleeding. The pain reduction studies were comprised of 225 patients while the postoperative bleeding studies included 3987 patients., Conclusions: Suturing tonsil pillars after tonsillectomy may be beneficial after cold tonsillectomy., Implications for Practice: Post-operative bleeding is one of the most common complications that can result in increased patient distress and hospitalization. In this article, we provide a literature review of tonsil pillar suturing and post-tonsillectomy hemorrhage. Our study suggests suturing the tonsil pillars immediately post-tonsillectomy may reduce the risk of severe post-operative bleeding requiring return to the operating room for certain patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bone adaptation is modulated by the timing, direction, rate and magnitude of mechanical loads. To investigate whether frequent slow, or infrequent fast, gaits could dominate bone adaptation to load, we compared scaling of the limb bones from two mammalian herbivore clades that use radically different high-speed gaits, bipedal hopping (suborder Macropodiformes; kangaroos and kin) and quadrupedal galloping (order Artiodactyla; goats, deer and kin). Forelimb and hindlimb bones were collected from 20 artiodactyl and 15 macropod species (body mass M 1.05-1536 kg) and scanned in computed tomography or X-ray microtomography. Second moment of area ( I max ) and bone length ( l ) were measured. Scaling relations ( y = ax b ) were calculated for l versus M for each bone and for I max versus M and I max versus l for every 5% of length. I max versus M scaling relationships were broadly similar between clades despite the macropod forelimb being nearly unloaded, and the hindlimb highly loaded, during bipedal hopping. I max versus l and l versus M scaling were related to locomotor and behavioural specializations. Low-intensity loads may be sufficient to maintain bone mass across a wide range of species. Occasional high-intensity gaits might not break through the load sensitivity saturation engendered by frequent low-intensity gaits., Competing Interests: The authors declare that we have no competing interests.