Efficacy and safety of tranexamic acid in the management of chronic subdural hematoma: a systematic review and meta-analysis.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition, particularly among the elderly. Various treatment options exist, but recurrence rates remain high. This systematic review and meta-analysis aims to assess the efficacy and safety of tranexamic acid (TXA) in the management of CSDH. METHODS: The authors conducted a comprehensive literature search adhering to the 2020 PRISMA guidelines, involving three primary databases (Scopus, PubMed, and Web of Science) that were searched for articles compiled from inception until October 20, 2023. The primary outcome was recurrence of CSDH, and secondary outcomes included complications and SDH volume following TXA treatment. The mean difference and odds ratios with 95% confidence intervals were calculated using the random-effects model. RESULTS: A total of 5 studies, involving 643 patients in the TXA group and 736 patients in the non-TXA group, met the inclusion criteria. The meta-analysis revealed that TXA use led to a significantly lower CSDH recurrence (OR 0.35, 95% CI 0.23-0.53; p < 0.01) without increasing complications (OR 1.84, 95% CI 0.43-7.95; p = 0.42). Additionally, TXA users had a significantly lower CSDH volume compared to the non-TXA group at 3-month follow-up (mean difference -4.56, 95% CI -8.76 to -0.36; p = 0.03). CONCLUSIONS: The findings suggest that TXA might be a promising agent for reducing the risk of CSDH recurrence without elevating the risk of complications. However, these results should be interpreted cautiously due to the limited number of studies included and the methodological heterogeneity. Further large-scale randomized controlled trials are needed to confirm these findings.

Image-Guided Navigation in Spine Surgery: From Historical Developments to Future Perspectives.

Intraoperative navigation is critical during spine surgery to ensure accurate instrumentation placement. From the early era of fluoroscopy to the current advancement in robotics, spinal navigation has continued to evolve. By understanding the variations in system protocols and their respective usage in the operating room, the surgeon can use and maximize the potential of various image guidance options more effectively. At the same time, maintaining navigation accuracy throughout the procedure is of the utmost importance, which can be confirmed intraoperatively by using an internal fiducial marker, as demonstrated herein. This technology can reduce the need for revision surgeries, minimize postoperative complications, and enhance the overall efficiency of operating rooms.

1-Piece Versus 2-Piece Fronto-Temporo-Orbito-Zygomatic Craniotomy: A Narrative Overview of Evolution.

BACKGROUND: The fronto-temporo-orbito-zygomatic (FTOZ) craniotomy is a commonly utilized surgical approach for many complex skull base lesions, especially lesions traversing skull base compartments. This craniotomy has evolved over multiple stages, originating from the classic pterional craniotomy and many variations that have emerged over time. METHODS: Few clinical and anatomic studies have both shaped these craniotomies as well as provided immense information about instances in which they are most useful. We review the origin and history of the one-piece and two-piece fronto-temporo-orbito-zygomatic craniotomy and deliberate their advantages and disadvantages. RESULTS: The FTOZ craniotomy provides access to the orbit as well as to multiple compartments in the cranium (anterior, middle and upper third posterior cranial fossae); thus, offering a multi-corridor approach to complex skull base lesions. The one-piece and two-piece fronto-temporo-orbitozygomatic craniotomies are two particularly notable variations that have stood the test of time. Selection between the two variations is mostly surgeon preference and comfort with the technique; however, there are certain indications that specifically suit each approach. Additionally, a pictorial review has been crafted to clearly illustrate the cuts to be made in both methods. CONCLUSION: Understanding the evolution of this craniotomy and surgical approach provides an insight into accessing complex skull base pathologies with minimal brain retraction via safe and viable corridors.

The feasibility of mechanical thrombectomy versus medical management for acute stroke with a large ischemic territory.

BACKGROUND: Mechanical thrombectomy (MT) for acute ischemic stroke is generally avoided when the expected infarction is large (defined as an Alberta Stroke Program Early CT Score of <6). OBJECTIVE: To perform a meta-analysis of recent trials comparing MT with best medical management (BMM) for treatment of acute ischemic stroke with large infarction territory, and then to determine the cost-effectiveness associated with those treatments. METHODS: A meta-analysis of the RESCUE-Japan, SELECT2, and ANGEL-ASPECT trials was conducted using R Studio. Statistical analysis employed the weighted average normal method for calculating mean differences from medians in continuous variables and the risk ratio for categorical variables. TreeAge software was used to construct a cost-effectiveness analysis model comparing MT with BMM in the treatment of ischemic stroke with large infarction territory. RESULTS: The meta-analysis showed significantly better functional outcomes, with higher rates of patients achieving a modified Rankin Scale score of 0-3 at 90 days with MT as compared with BMM. In the base-case analysis using a lifetime horizon, MT led to a greater gain in quality-adjusted life-years (QALYs) of 3.46 at a lower cost of US$339 202 in comparison with BMM, which led to the gain of 2.41 QALYs at a cost of US$361 896. The incremental cost-effectiveness ratio was US$-21 660, indicating that MT was the dominant treatment at a willingness-to-pay of US$70 000. CONCLUSIONS: This study shows that, besides having a better functional outcome at 90-days' follow-up, MT was more cost-effective than BMM, when accounting for healthcare cost associated with treatment outcome.

Utilization of Locum Tenens in Neurosurgery.

INTRODUCTION: Despite its rising popularity, little has been described about locum tenens employment (locums) in neurosurgery. This study provides the first nationwide overview of the locums neurosurgery experience. METHODS: An anonymous online survey examined practice characteristics of respondents, extent of and satisfaction with locums, motivations for pursuing locums, case volumes, agencies used, compensation, and positive/negative aspects of experiences. Responses were collected between November 2020 and February 2021. RESULTS: Response rate for the 1852 neurosurgeons who opened the survey request was 4.9%; 36 of 91 respondents had previously worked locums and were commonly motivated by compensation or transitioning to new jobs or retirement. In our response group, 92% of locums respondents had taken more than one position and 47% had taken more than 10. Neurosurgeons performing <200 cases/year were significantly more likely to have also worked locums than those performing >200 cases/year (41.6% locums, 12.7% non-locums, P = 0.001). Responses showed that 69% of locums respondents earned $2000-$2999/day and 16% earned >$3500/day. Nearly 78% of locums respondents were satisfied with their experience(s) and 86% would take another future locums position. Being in practice for >15 years was significantly associated with satisfaction with locums (P = 0.03). Reported flaws included unfamiliarity with hospitals, limited continuity of care, credentialing burdens, and inadequate travel compensation. CONCLUSIONS: Locums is utilized by neurosurgeons across multiple practice types and may serve to complement workloads or "fill in gaps" between longer-term employment. Overall, locums neurosurgeons are well compensated, and the majority are satisfied with their experience(s). Inevitably, flaws still exist with locums employment, which may be the focus of organized efforts aiming to improve the experience.

Factors impacting neurosurgery residents' operative case volume: a nationwide survey.

OBJECTIVE: Neurological surgery residency remains one of the most competitive and longest specialties in terms of training in medicine. The Accreditation Council for Graduate Medical Education uses residents' case volume throughout residency as one of its measures for the quality of surgical training. The objective was to study the variability of residency case volume among US training programs and to analyze the factors that potentially influence that case volume. METHODS: In line with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) guidelines, an online survey regarding department size, case volume, number of residents per year, number of dedicated research years, presence of fellows, and resident case volume by the time of graduation was created using Google Forms and distributed to all neurosurgery residency program directors and coordinators in the US. RESULTS: A total of 97 of the 115 programs (84.3%) responded to the survey. Fifteen programs were excluded due to missing data or incomplete resident cohort at the time of the survey, and a total of 82 programs were included in the analysis. The average number of cases performed by residents as lead or senior surgeons by the time of graduation ranged from 900 to 2250 (median 1600 cases). The resident case volume did not have a significant correlation with the program case volume, number of operating attending neurosurgeons, number of residents, number of research years, or presence of fellows. The only factor that impacted the resident case volume was the number of cases performed per faculty. CONCLUSIONS: The number of cases performed by residents throughout residency varied significantly between programs. Although other factors play important roles in the quality of training, including autonomy, variation, and complexity of cases, the resident case volume is one of the only measurable factors. This study sheds some light on the factors that potentially influence neurosurgical resident case volume.

Application of Machine Learning Strategies to Model the Effects of Sevoflurane on Somatosensory-Evoked Potentials during Spine Surgery.

In this study, a small sample of patients' neuromonitoring data was analyzed using machine learning (ML) tools to provide proof of concept for quantifying complex signals. Intraoperative neurophysiological monitoring (IONM) is a valuable asset for monitoring the neurological status of a patient during spine surgery. Notably, this technology, when operated by neurophysiologists and surgeons familiar with proper alarm criteria, is capable of detecting neurological deficits. However, non-surgical factors, such as volatile anesthetics like sevoflurane, can negatively influence robust IONM signal generation. While sevoflurane has been shown to affect the latency and amplitude of somatosensory evoked potential (SSEP), a more complex and nuanced analysis of the SSEP waveform has not been performed. In this study, signal processing and machine learning techniques were used to more intricately characterize and predict SSEP waveform changes as a function of varying end-tidal sevoflurane concentration. With data from ten patients who underwent spinal procedures, features describing the SSEP waveforms were generated using principal component analysis (PCA), phase space curves (PSC), and time-frequency analysis (TFA). A minimum redundancy maximum relevance (MRMR) feature selection technique was then used to identify the most important SSEP features associated with changing sevoflurane concentrations. Once the features carrying the maximum amount of information about the majority of signal waveform variability were identified, ML models were used to predict future changes in SSEP waveforms. Linear regression, regression trees, support vector machines, and neural network ML models were then selected for testing. Using SSEP data from eight patients, the models were trained using a range of features selected during MRMR calculations. During the training phase of model development, the highest performing models were identified as support vector machines and regression trees. After identifying the highest performing models for each nerve group, we tested these models using the remaining two patients' data. We compared the models' performance metrics using the root mean square error values (RMSEs). The feasibility of the methodology described provides a general framework for the applications of machine learning strategies to further delineate the effects of surgical and non-surgical factors affecting IONM signals.

Pathophysiology, Management, and Therapeutics in Subarachnoid Hemorrhage and Delayed Cerebral Ischemia: An Overview.

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke resulting from the rupture of an arterial vessel within the brain. Unlike other stroke types, SAH affects both young adults (mid-40s) and the geriatric population. Patients with SAH often experience significant neurological deficits, leading to a substantial societal burden in terms of lost potential years of life. This review provides a comprehensive overview of SAH, examining its development across different stages (early, intermediate, and late) and highlighting the pathophysiological and pathohistological processes specific to each phase. The clinical management of SAH is also explored, focusing on tailored treatments and interventions to address the unique pathological changes that occur during each stage. Additionally, the paper reviews current treatment modalities and pharmacological interventions based on the evolving guidelines provided by the American Heart Association (AHA). Recent advances in our understanding of SAH will facilitate clinicians' improved management of SAH to reduce the incidence of delayed cerebral ischemia in patients.

The Use of Intraoperative Neuromonitoring for Cervical Spine Surgery: Indications, Challenges, and Advances.

Intraoperative neuromonitoring (IONM) has become an indispensable surgical adjunct in cervical spine procedures to minimize surgical complications. Understanding the historical development of IONM, indications for use, associated pitfalls, and recent developments will allow the surgeon to better utilize this important technology. While IONM has shown great promise in procedures for cervical deformity, intradural tumors, or myelopathy, routine use in all cervical spine cases with moderate pathology remains controversial. Pitfalls that need to be addressed include human error, a lack of efficient communication, variable alarm warning criteria, and a non-standardized checklist protocol. As the techniques associated with IONM technology become more robust moving forward, IONM emerges as a crucial solution to updating patient safety protocols.

An Anatomic Assessment of the Intercavernous Sinuses and Review of the Literature.

Introduction As expanded endoscopic endonasal approaches are gaining popularity, a thorough understanding of the anatomy of the intercavernous sinuses is pertinent to avoid bleeding complications. There have been few studies reporting the presence and dimensions of the anterior intercavernous sinus (AIS), posterior intercavernous sinus (PIS), and inferior intercavernous sinus (IIS). We performed a cadaveric study to better understand these structures. Methods Colored latex was injected into the arterial and venous trees of 17 cadaveric heads. Dissections assessed the presence and dimensions of the AIS, PIS, and IIS. In an additional three specimens, the sellar contents were subjected to histological analysis. Results Of the 20 total specimens, 13 (65%) demonstrated the gross presence of all three sinuses. In six specimens (30%), only the AIS and PIS could be identified, and in one specimen, only an AIS and IIS were identified. An AIS was identified in all 20 (100%) specimens, PIS in 18 (88%), and an IIS in 14 (70%). In two specimens (10%), the AIS covered the entire face of the sella. Dimensions of the AIS averaged 1.7 × 11.7 × 2.8 mm, PIS averaged 1.5 × 10.8 × 1.7 mm, and IIS averaged 8.7 × 11.8 × 1.0 mm when present. Conclusion All examined specimens demonstrated the presence of an AIS, and most had a PIS. The presence of an IIS was more variable. Preoperative awareness of these sinuses is helpful in planning transsphenoidal surgery to minimize the risk of bleeding.

PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury.

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of fission and fusion. Overall, these pathophysiological findings correlated with decreased protein arginine methyltransferase 7 (PRMT7) protein levels and activity post-rmTBI. Here, we increased PRMT7 levels in vivo to assess the role of the neurovasculature and mitochondria post-rmTBI. In vivo overexpression of PRMT7 using a neuronal specific AAV vector led to restoration of neurovascular coupling, prevented BBB leakage, and promoted mitochondrial respiration, altogether to suggest a protective and functional role of PRMT7 in rmTBI.

A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury.

Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation. Furthermore, microglia were assessed via enhanced iba1 protein levels and morphological changes using immunofluorescence. In addition, LC/MS analyses revealed excess glutamate production, as well as diffuse axonal injury via Bielschowsky's silver stain kit. Moreover, the heterogeneous nature of rmTBI has made it challenging to identify drug therapies that address rmTBI, therefore we sought to identify novel targets in the concurrent rmTBI pathology. The pathophysiological findings correlated with a time-dependent decrease in protein arginine methyltransferase 7 (PRMT7) protein expression and activity post-rmTBI along with dysregulation of PRMT upstream mediators s-adenosylmethionine and methionine adenosyltransferase 2 (MAT2) in vivo. In addition, inhibition of the upstream mediator MAT2A using the HT22 hippocampal neuronal cell line suggest a mechanistic role for PRMT7 via MAT2A in vitro. Collectively, we have identified PRMT7 as a novel target in rmTBI pathology in vivo and a mechanistic link between PRMT7 and upstream mediator MAT2A in vitro.

Health inequities and socioeconomic factors predicting the access to treatment for unruptured intracranial aneurysms in the USA in the last 20 years: interaction effect of race, gender, and insurance.

BACKGROUND: The literature suggests that minority racial and ethnic groups have lower treatment rates for unruptured intracranial aneurysms (UIA). It is uncertain how these disparities have changed over time. METHODS: A cross-sectional study using the National Inpatient Sample database covering 97% of the USA population was carried out. RESULTS: A total of 213 350 treated patients with UIA were included in the final analysis and compared with 173 375 treated patients with aneurysmal subarachnoid hemorrhage (aSAH) over the years 2000-2019. The mean (SD) age of the UIA and aSAH groups was 56.8 (12.6) years and 54.3 (14.1) years, respectively. In the UIA group, 60.7% were white patients, 10.2% were black patients, 8.6% were Hispanic, 2% were Asian or Pacific Islander, 0.5% were Native Americans, and 2.8% were others. The aSAH group comprised 48.5% white patients, 13.6% black patients, 11.2% Hispanics, 3.6% Asian or Pacific Islanders, 0.4% Native Americans, and 3.7% others. After adjusting for covariates, black patients (OR 0.637, 95% CI 0.625 to 0.648) and Hispanic patients (OR 0.654, 95% CI 0.641 to 0.667) had lower odds of treatment compared with white patients. Medicare patients had higher odds of treatment than private patients, while Medicaid and uninsured patients had lower odds. Interaction analysis showed that non-white/Hispanic patients with any insurance/no insurance had lower treatment odds than white patients. Multivariable regression analysis showed that the treatment odds of black patients has improved slightly over time, while the odds for Hispanic patients and other minorities have remained the same over time. CONCLUSION: This study from 2000 to 2019 shows that disparities in the treatment of UIA have persisted but have slightly improved over time for black patients while remaining constant for Hispanic patients and other minority groups.

Microsurgical clipping and endovascular management of unruptured anterior circulation aneurysms: how age, frailty, and comorbidity indexes influence outcomes.

OBJECTIVE: Frailty is one of the important factors in predicting the outcomes of surgery. Many surgical specialties have adopted a frailty assessment in the preoperative period for prognostication; however, there are limited data on the effects of frailty on the outcomes of cerebral aneurysms. The object of this study was to find the effect of frailty on the surgical outcomes of anterior circulation unruptured intracranial aneurysms (UIAs) and compare the frailty index with other comorbidity indexes. METHODS: A retrospective study was performed utilizing the National Inpatient Sample (NIS) database (2016-2018). The Hospital Frailty Risk Score (HFRS) was used to assess frailty. On the basis of the HFRS, the whole cohort was divided into low-risk (0-5), intermediate-risk (> 5 to 15), and high-risk (> 15) frailty groups. The analyzed outcomes were nonhome discharge, complication rate, extended length of stay, and in-hospital mortality. RESULTS: In total, 37,685 patients were included in the analysis, 5820 of whom had undergone open surgical clipping and 31,865 of whom had undergone endovascular management. Mean age was higher in the high-risk frailty group than in the low-risk group for both clipping (63 vs 55.4 years) and coiling (64.6 vs 57.9 years). The complication rate for open surgical clipping in the high-risk frailty group was 56.1% compared to 0.8% in the low-risk group. Similarly, for endovascular management, the complication rate was 60.6% in the high-risk group compared to 0.3% in the low-risk group. Nonhome discharges were more common in the high-risk group than in the low-risk group for both open clipping (87.8% vs 19.7%) and endovascular management (73.1% vs 4.4%). Mean hospital charges for clipping were $341,379 in the high-risk group compared to $116,892 in the low-risk group. Mean hospital charges for coiling were $392,861 in the high-risk frailty group and $125,336 in the low-risk group. Extended length of stay occurred more frequently in the high-risk frailty group than in the low-risk group for both clipping (82.9% vs 10.7%) and coiling (94.2% vs 12.7%). Frailty had higher area under the receiver operating characteristic curve values than those for other comorbidity indexes and age in predicting outcomes. CONCLUSIONS: Frailty affects surgical outcomes significantly and outperforms age and other comorbidity indexes in predicting outcome. It is imperative to include frailty assessment in preoperative planning.

Racial and socioeconomic disparities in the advanced treatment of medically intractable pediatric epilepsy.

OBJECTIVE: Racial and ethnic disparities in healthcare have gained significant importance since the Institute of Medicine published its report on disparities in healthcare. There is a lack of evidence on how race and ethnicity affect access to advanced treatment of pediatric medically intractable epilepsy. In this context, the authors analyzed the latest Kids' Inpatient Database (KID) for racial/ethnic disparities in access to surgical treatment of epilepsy. METHODS: The authors queried the KID for the years 2016 and 2019 for the diagnosis of medically intractable epilepsy. RESULTS: A total of 29,292 patients were included in the sample. Of these patients, 8.9% (n = 2610) underwent surgical treatment/invasive monitoring. The mean ages in the surgical treatment and nonsurgical treatment groups were 11.73 years (SD 5.75 years) and 9.5 years (SD 6.16 years), respectively. The most common insurance in the surgical group was private/commercial (55.9%) and Medicaid in the nonsurgical group (47.7%) (p < 0.001). White patients accounted for the most common population in both groups, followed by Hispanic patients. African American patients made up 7.9% in the surgical treatment group compared with 12.9% in the nonsurgical group. African American (41.1%) and Hispanic (29.9%) patients had higher rates of emergency department (ED) utilization compared with the White population (24.6%). After adjusting for all covariates, the odds of surgical treatment increased with increasing age (OR 1.06, 95% CI 1.053-1.067; p < 0.001). African American race (OR 0.513, 95% CI 0.443-0.605; p < 0.001), Hispanic ethnicity (OR 0.681, 95% CI 0.612-0.758; p < 0.001), and other races (OR 0.789, 95% CI 0.689-0.903; p = 0.006) had lower surgical treatment odds compared with the White population. Medicaid/Medicare was associated with lower surgical treatment odds than private/commercial insurance (OR 0.603, 0.554-0.657; p < 0.001). Interaction analysis revealed that African American (OR 0.708, 95% CI 0.569-0.880; p = 0.001) and Hispanic (OR 0.671, 95% CI 0.556-0.809; p < 0.001) populations with private insurance had lower surgical treatment odds than White populations with private insurance. Similarly, African American patients, Hispanic patients, and patients of other races with nonprivate insurance also had lower surgical treatment odds than their White counterparts after adjusting for all other covariates. CONCLUSIONS: Based on the KID, African American and Hispanic populations had lower surgical treatment rates than their White counterparts, with higher utilization of the ED for pediatric medically intractable epilepsy.