Multiplicative effect of frailty and obesity on postoperative mortality following spine surgery: a deep dive into the frailty, obesity, and Clavien-Dindo dynamic.

BACKGROUND/OBJECTIVES: Obesity is a global health challenge that affects a large proportion of adults worldwide. Obesity and frailty pose considerable health risks due to their potential to interact and amplify one another's negative effects. Therefore, we sought to compare the discriminatory thresholds of the risk analysis index (RAI), 5-factor modified frailty index (m-FI-5) and patient age for the primary endpoint of postoperative mortality. SUBJECTS/METHODS: We included spine surgery patients ≥18 years old, from the American College of Surgeons National Quality Improvement program database from 2012-2020, that were classified as obese. We performed receiver operating characteristic curve analysis to compare the discrimination threshold of RAI, mFI-5, and patient age for postoperative mortality. Proportional hazards risk-adjusted regressions were performed, and Hazard ratios and corresponding 95% Confidence intervals (CI) are reported. RESULTS: Overall, there were 149 163 patients evaluated, and in the ROC analysis for postoperative mortality, RAI showed superior discrimination C-statistic 0.793 (95%CI: 0.773-0.813), compared to mFI-5 C-statistic 0.671 (95%CI 0.650-0.691), and patient age C-statistic 0.686 (95%CI 0.666-0.707). Risk-adjusted analyses were performed, and the RAI had a stepwise increasing effect size across frailty strata: typical patients HR 2.55 (95%CI 2.03-3.19), frail patients HR 3.48 (95%CI 2.49-4.86), and very frail patients HR 4.90 (95%CI 2.87-8.37). We found increasing postoperative mortality effect sizes within Clavein-Dindo complication strata, consistent across obesity categories, exponentially increasing with frailty, and multiplicatively enhanced within CD, frailty and obesity strata. CONCLUSION: In this study of 149 163 patients classified as obese and undergoing spine procedures in an international prospective surgical database, the RAI demonstrated superior discrimination compared to the mFI-5 and patient age in predicting postoperative mortality risk. The deleterious effects of frailty and obesity were synergistic as their combined effect predicted worse outcomes.

The risk analysis index demonstrates exceptional discrimination in predicting frailty's impact on neurosurgical length of stay quality metrics.

BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.

Preoperative Frailty Predicts Worse Outcomes after Microvascular Decompression for Trigeminal Neuralgia, Hemifacial Spasm, and Glossopharyngeal Neuralgia: A Multicenter Analysis of 1,473 Patients from a Prospective Surgical Registry.

INTRODUCTION: Microvascular decompression (MVD) is an efficacious neurosurgical intervention for patients with medically intractable neurovascular compression syndromes. However, MVD may occasionally cause life-threatening or altering complications, particularly in patients unfit for surgical operations. Recent literature suggests a lack of association between chronological age and surgical outcomes for MVD. The Risk Analysis Index (RAI) is a validated frailty tool for surgical populations (both clinical and large database). The present study sought to evaluate the prognostic ability of frailty, as measured by RAI, to predict outcomes for patients undergoing MVD from a large multicenter surgical registry. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2011-2020) was queried using diagnosis/procedure codes for patients undergoing MVD procedures for trigeminal neuralgia (n = 1,211), hemifacial spasm (n = 236), or glossopharyngeal neuralgia (n = 26). The relationship between preoperative frailty (measured by RAI and 5-factor modified frailty index [mFI-5]) for primary endpoint of adverse discharge outcome (AD) was analyzed. AD was defined as discharge to a facility which was not home, hospice, or death within 30 days. Discriminatory accuracy for prediction of AD was assessed by computation of C-statistics (with 95% confidence interval) from receiver operating characteristic (ROC) curve analysis. RESULTS: Patients undergoing MVD (N = 1,473) were stratified by RAI frailty bins: 71% with RAI 0-20, 28% with RAI 21-30, and 1.2% with RAI 31+. Compared to RAI score 19 and below, RAI 20 and above had significantly higher rates of postoperative major complications (2.8% vs. 1.1%, p = 0.01), Clavien-Dindo grade IV complications (2.8% vs. 0.7%, p = 0.001), and AD (6.1% vs. 1.0%, p < 0.001). The rate of primary endpoint was 2.4% (N = 36) and was positively associated with increasing frailty tier: 1.5% in 0-20, 5.8% in 21-30, and 11.8% in 31+. RAI score demonstrated excellent discriminatory accuracy for primary endpoint in ROC analysis (C-statistic: 0.77, 95% CI: 0.74-0.79) and demonstrated superior discrimination compared to mFI-5 (C-statistic: 0.64, 95% CI: 0.61-0.66) (DeLong pairwise test, p = 0.003). CONCLUSIONS: This was the first study to link preoperative frailty to worse surgical outcomes after MVD surgery. RAI frailty score predicts AD after MVD with excellent discrimination and holds promise for preoperative counseling and risk stratification of surgical candidates. A risk assessment tool was developed and deployed with a user-friendly calculator: https://nsgyfrailtyoutcomeslab.shinyapps.io/microvascularDecompression.

Failure to rescue as a patient safety indicator for neurosurgical patients: are we there yet? A systematic review.

Failure to rescue (FTR) is a standardized patient safety indicator (PSI-04) developed by the Agency for Healthcare Research and Quality (AHRQ) to assess the ability of a healthcare team to prevent mortality following a major complication. However, FTR rates vary and are impacted by non-modifiable individual patient characteristics such as baseline frailty. This raises concerns regarding the validity of FTR as an objective quality metric, as not all patients have the same baseline frailty level, or physiological reserve, to recover from major complications. Literature from other surgical specialties has identified flaws in FTR and called for risk-adjusted metrics. Currently, knowledge of factors influencing FTR and its subsequent implementation in neurosurgical patients are limited. The present review assesses trends in FTR utilization to assess how FTR performs as an objective neurosurgery quality metric. This review then proposes how FTR may be best modified to optimize use in neurosurgical patients. A PubMed search was performed to identify articles published until August 9, 2023. Studies that reported FTR as an outcome in patients undergoing neurosurgical procedures were included. A qualitative assessment was performed using the Newcastle Ottawa Scale (NOS). The initial search revealed 1232 citations. After a title and abstract screen, followed by a full text screen, 12 studies met criteria for inclusion. These articles measured FTR across a total of 764,349 patients undergoing neurosurgical procedures. Five studies analyzed FTR with regard to hospital characteristics, and three studies utilized patient characteristics to predict FTR. All studies were considered high quality based on the NOS. Modifications in criteria to measure FTR are necessary since FTR depends on patient characteristics like frailty. This would allow for the incorporation of risk-adjusted FTR metrics that would aid in clinical decision making in neurosurgical patients.

Preoperative frailty and 30-day mortality after resection of brain metastases: a multicenter surgical registry analysis of 11,038 patients.

OBJECTIVE: Surgery plays a key role in the management of brain metastases. Stratifying surgical risk and individualizing treatment will help optimize outcomes because there is clinical equipoise between radiation and resection as treatment options for many patients. Here, the authors used a multicenter database to assess the prognostic utility of baseline frailty, calculated with the Risk Analysis Index (RAI), for prediction of mortality within 30 days after surgery for brain metastasis. METHODS: The authors pooled patients who had been surgically treated for brain metastasis from the American College of Surgeons National Surgical Quality Improvement Program database (2012-2020). The authors studied the relationship between preoperative calculated RAI score and 30-day mortality after surgery for brain metastasis by using linear-by-linear proportional trend tests and binary logistic regression. The authors calculated C-statistics (with 95% CIs) in receiver operating characteristic (ROC) curve analysis to assess discriminative accuracy. RESULTS: The authors identified 11,038 patients who underwent brain metastasis resection with a median (interquartile range) age of 62 (54-69) years. The authors categorized patients into four groups on the basis of RAI: robust (RAI 0-20), 8.1% of patients; normal (RAI 21-30), 9.2%; frail (RAI 31-40), 75%; and severely frail (RAI ≥ 41), 8.1%. The authors found a positive correlation between 30-day mortality and frailty. RAI demonstrated superior predictive discrimination for 30-day mortality as compared with the 5-factor modified frailty index (mFI-5) on ROC analysis (C-statistic 0.65, 95% CI 0.65-0.66). CONCLUSIONS: The RAI frailty score accurately estimates 30-day mortality after brain metastasis resection and can be calculated online with an open-access software tool: https://nsgyfrailtyoutcomeslab.shinyapps.io/BrainMetsResection/. Accordingly, RAI can be utilized to measure surgical risk, guide treatment options, and optimize outcomes for patients with brain metastases. RAI has superior discrimination for predicting 30-day mortality compared with mFI-5.

Thirty-day outcomes for suboccipital decompression in adults with Chiari malformation type I: a frailty-driven perspective from the American College of Surgeons National Surgical Quality Improvement Program.

OBJECTIVE: When indicated, patients with symptomatic Chiari malformation type I (CM-I) may benefit from suboccipital decompression (SOD). Although SOD is considered a lower-risk neurosurgical procedure, preoperative risk assessment and careful surgical patient selection remain critical. The objectives of the present study were twofold: 1) describe 30-day SOD outcomes for CM patients with attention to the impact of preoperative frailty and 2) design a predictive model for the primary endpoint of nonhome discharge (NHD). METHODS: There were 1015 CM-I patients who underwent SOD in the 2011-2020 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, as specified by diagnostic and procedural codes (Current Procedural Terminology code 61343). Descriptive statistics were used to analyze total cohort baseline demographics, preoperative comorbidities, and postoperative outcomes within 30 days of surgery. Univariate cross-tabulation was used to compare baseline demographics and preoperative characteristics across the NHD and home discharge (HD) cohorts. Receiver operating characteristic (ROC) curve analysis was used to assess the discriminative ability of the revised Risk Analysis Index (RAI-rev) on NHD. RESULTS: The study cohort had a median age of 36 years, and 80.6% of patients were female. Race distribution was categorized as White (69.9%), Black (16.6%), and other groups (13.6%). The most common preoperative comorbidities were active smoking (24.4%), hypertension (19.2%), and diabetes mellitus (4.7%). The primary outcome of NHD occurred in 4.6% of patients (n = 47). Increasing frailty (measured by the RAI-rev) was associated with a stepwise increase in the rate of NHD: 2.3% for RAI-rev scores 0-10, 5.8% for RAI-rev scores 11-15, 7.6% for RAI-rev scores 16-20, 18.2% for RAI-rev scores 21-25, and 77.8% for RAI-rev scores ≥ 26 (p < 0.001). Other preoperative factors associated with NHD included older age, nonelective surgery, diabetes, hypertension, and elevated creatinine (all p < 0.01). The other most common 30-day complications included unplanned readmission (9.3%), unplanned reoperation (5.3%), return to the operating room (5.8%), Clavien-Dindo grade IV (life-threatening) (1.5%), organ space surgical site infection (SSI) (1.5%), superficial SSI (1.4%), and reoperation for a CSF leak (1.1%). Surgical mortality (within 30 days) was extremely rare (1/1015, 0.1%). ROC curve analysis demonstrated that RAI-rev predicted NHD with significant discriminatory accuracy among CM-I patients who received SOD treatment (C-statistic 0.731, 95% CI 0.648-0.814). CONCLUSIONS: This decade-long analysis of a multicenter surgical registry provides internationally representative, modern rates of 30-day outcomes after suboccipital decompression (with or without duraplasty) for adult CM-I patients. Preoperative frailty assessment with the RAI-rev may help identify higher-risk surgical candidates.

Gender concordance and publication productivity within Neurosurgical Focus: a 10-year review (2013-2022).

OBJECTIVE: The "leaky academic pipeline" describes how female representation in leadership positions has remained stagnant despite an increase in the number of female trainees. Female mentorship to female mentees, and female role models at higher academic positions have been shown to positively influence academic productivity. To the authors' knowledge, the impact of female editorial board representation on authorship trends in neurosurgical journals remains undescribed. This study aimed to analyze trends in the representation of female topic editors and its impact on female authorship within Neurosurgical Focus over a 10-year period. METHODS: Publicly available data were collected from the journal's website, inclusive from January 2013 to December 2022. The articles were grouped into technical and nontechnical themes based on their relevance to specific technical details regarding surgical techniques. Female gender-concordant publications were defined as publications having a female first author (or co-first author) and a female senior author. Linear regression analysis determined trends in publishing. Odds ratios and 95% CIs were calculated using logistic regression analysis. Pearson correlation and cross-correlation analyses were used to examine each pairwise comparison of time series. The statistical significance of associations was evaluated using t-tests and chi-square and Fisher's exact tests. RESULTS: The number of female topic editors and gender-concordant authors increased over time (p < 0.05). Women accounted for ≥ 50% of the topic editors on nontechnical themes relevant to education and gender diversity. Having a female senior author was associated with higher publication productivity for original research and review articles among female authors (OR 13.73, 95% CI 1.75-394.31; p < 0.05). Female authors had higher odds of publishing editorials with a female topic editor (OR 3.81, 95% CI 1.37-11.02; p < 0.01). Publications with female first and senior authors were significantly more likely to have female topic editors (OR 4.05, 95% CI 1.38-12.92; p < 0.01). A positive association was observed between female senior authors and female topic editors at lag -8, with a correlation coefficient of 0.19 (p = 0.03). CONCLUSIONS: Female attending-to-female trainee mentorship and female representation among editorial boards play a crucial role in enhancing academic productivity among women. Efforts to sustain academic productivity during the early-career period would presumably help increase female representation in neurosurgery.

Frailty as a Superior Predictor of Dysphagia and Surgically Placed Feeding Tube Requirement After Anterior Cervical Discectomy and Fusion Relative to Age.

Frailty is a measure of physiological reserve that has been demonstrated to be a discriminative predictor of worse outcomes across multiple surgical subspecialties. Anterior cervical discectomy and fusion (ACDF) is one of the most common neurosurgical procedures in the United States and has a high incidence of postoperative dysphagia. To determine the association between frailty and dysphagia after ACDF and compare the predictive value of frailty and age. 155,300 patients with cervical stenosis (CS) who received ACDF were selected from the 2016-2019 National Inpatient Sample (NIS) utilizing International Classification of Disease, tenth edition (ICD-10) codes. The 11-point modified frailty index (mFI-11) was used to stratify patients based on frailty: mFI-11 = 0 was robust, mFI-11 = 1 was prefrail, mFI-11 = 2 was frail, and mFI-11 = 3 + was characterized as severely frail. Demographics, complications, and outcomes were compared between frailty groups. A total of 155,300 patients undergoing ACDF for CS were identified, 33,475 (21.6%) of whom were frail. Dysphagia occurred in 11,065 (7.1%) of all patients, and its incidence was significantly higher for frail patients (OR 1.569, p < 0.001). Frailty was a risk factor for postoperative complications (OR 1.681, p < 0.001). Increasing frailty and undergoing multilevel ACDF were significant independent predictors of negative postoperative outcomes, including dysphagia, surgically placed feeding tube (SPFT), prolonged LOS, non-home discharge, inpatient death, and increased total charges (p < 0.001 for all). Increasing mFI-11 score has better prognostic value than patient age in predicting postoperative dysphagia and SPFT after ACDF.

Preoperative meningioma embolization reduces perioperative blood loss: a multi-center retrospective matched case-control study.

BACKGROUND AND PURPOSE: The utility of preoperative embolization remains controversial within the literature. Here, we evaluate whether preoperative meningioma embolization is effective in reducing intraoperative blood loss, safe to perform, and cost-effective when compared with surgical resection without preoperative embolization. METHODS: Twenty-nine patients with meningiomas were matched by tumor size and location to 29 control patients with meningiomas at another institution where preoperative embolization was not practiced. The variables evaluated were pre- and post-operative hemoglobin and hematocrit levels as a measure of operative blood loss and postoperative morbidity. The additional cost of undergoing angiography and embolization was calculated from hospital charges obtained from the billing department. RESULTS: The mean decrease in perioperative hemoglobin and hematocrit was 0.9 and 2.7, respectively, in the embolization group and 2.8 and 10.0, respectively, in the control group for a significant decrease in operative blood loss as measured by change in hematocrit and hemoglobin levels after surgery. There was no significant difference in operative blood loss when subdividing patients based on tumor location. There were no angiogram-related complications. Twenty-two of 29 patients (76%) underwent embolization of a feeding artery, whereas 7 patients underwent only a diagnostic angiogram. The mean additional charge per patient in the embolization group was $88,767. CONCLUSIONS: Preoperative embolization was safe and effective in reducing the overall perioperative blood loss in patients undergoing meningioma resection, as measured by the change in postoperative hemoglobin and hematocrit levels. However, the cost of embolization was significant.

Preoperative frailty measured by risk analysis index predicts complications and poor discharge outcomes after Brain Tumor Resection in a large multi-center analysis.

PURPOSE: To evaluate the independent effect of frailty, as measured by the Risk Analysis Index-Administrative (RAI-A) for postoperative complications and discharge outcomes following brain tumor resection (BTR) in a large multi-center analysis. METHODS: Patients undergoing BTR were queried from the National Surgical Quality Improvement Program (NSIQP) for the years 2015 to 2019. Multivariable logistic regression was performed to evaluate the independent associations between frailty tools (age, 5-factor modified frailty score [mFI-5], and RAI-A) on postoperative complications and discharge outcomes. RESULTS: We identified 30,951 patients who underwent craniotomy for BTR; the median age of our study sample was 59 (IQR 47-68) years old and 47.8% of patients were male. Overall, increasing RAI-A score, in an overall stepwise fashion, was associated with increasing risk of adverse outcomes including in-hospital mortality, non-routine discharge, major complications, Clavien-Dindo Grade IV complication, and extended length of stay. Multivariable regression analysis (adjusting for age, sex, BMI, non-elective surgery status, race, and ethnicity) demonstrated that RAI-A was an independent predictor for worse BTR outcomes. The RAI-A tiers 41-45 (1.2% cohort) and > 45 (0.3% cohort) were ~ 4 (Odds Ratio [OR]: 4.3, 95% CI: 2.1-8.9) and ~ 9 (OR: 9.5, 95% CI: 3.9-22.9) times more likely to have in-hospital mortality compared to RAI-A 0-20 (34% cohort). CONCLUSIONS AND RELEVANCE: Increasing preoperative frailty as measured by the RAI-A score is independently associated with increased risk of complications and adverse discharge outcomes after BTR. The RAI-A may help providers present better preoperative risk assessment for patients and families weighing the risks and benefits of potential BTR.

Rapid exponential increase in neurosurgery departmental scholarly output following an intensive research initiative.

There has been extensive research into methods of increasing academic departmental scholarly activity (DSA) through targeted interventions. Residency programmes are responsible for ensuring sufficient scholarly opportunities for residents. We sought to discover the outcomes of an intensive research initiative (IRI) on DSA in our department in a short-time interval. IRI was implemented, consisting of multiple interventions, to rapidly produce an increase in DSA through resident/medical student faculty engagement. We compare pre-IRI (8 years) and post-IRI (2 years) research products (RP), defined as the sum of oral presentations and publications, to evaluate the IRI. The study was performed in 2020. The IRI resulted in an exponential increase in DSA with an annual RP increase of 350% from 2017 (3 RP) to 2018 (14 RP), with another 92% from 2018 (14 RP) to 2019 (27 RP). RP/year exponentially increased from 2.1/year to 10.5/year for residents and 0.5/year to 10/year for medical students, resulting in a 400% and 1900% increase in RP/year, respectively. The common methods in literature to increase DSA included instituting protected research time (23.8%) and research curriculum (21.5%). We share our department's increase in DSA over a short 2-year period after implementing our IRI. Our goal in reporting our experience is to provide an example for departments that need to rapidly increase their DSA. By reporting the shortest time interval to achieve exponential DSA growth, we hope this example can support programmes in petitioning hospitals and medical colleges for academic support resources.

Preoperative risk model for perioperative stroke after intracranial tumor resection: ACS NSQIP analysis of 30,951 cases.

OBJECTIVE: Perioperative and/or postoperative cerebrovascular accidents (PCVAs) after intracranial tumor resection (ITR) are serious complications with devastating effects on quality of life and survival. Here, the authors retrospectively analyzed a prospectively maintained, multicenter surgical registry to design a risk model for PCVA after ITR to support efforts in neurosurgical personalized medicine to risk stratify patients and potentially mitigate poor outcomes. METHODS: The National Surgical Quality Improvement Program database was queried for ITR cases (2015-2019, n = 30,951). Patients with and without PCVAs were compared on baseline demographics, preoperative clinical characteristics, and outcomes. Frailty (physiological reserve for surgery) was measured by the Revised Risk Analysis Index (RAI-rev). Logistic regression analysis was performed to identify independent associations between preoperative covariates and PCVA occurrence. The ITR-PCVA risk model was generated based on logit effect sizes and assessed in area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: The rate of PCVA was 1.7% (n = 532). Patients with PCVAs, on average, were older and frailer, and had increased rates of nonelective surgery, interhospital transfer status, diabetes, hypertension, unintentional weight loss, and elevated BUN. PCVA was associated with higher rates of postoperative reintubation, infection, thromboembolic events, prolonged length of stay, readmission, reoperation, nonhome discharge destination, and 30-day mortality (all p < 0.001). In multivariable analysis, predictors of PCVAs included RAI "frail" category (OR 1.7, 95% CI 1.2-2.4; p = 0.006), Black (vs White) race (OR 1.5, 95% CI 1.1-2.1; p = 0.009), nonelective surgery (OR 1.4, 95% CI 1.1-1.7; p = 0.003), diabetes mellitus (OR 1.5, 95% CI 1.1-1.9; p = 0.002), hypertension (OR 1.4, 95% CI 1.1-1.7; p = 0.006), and preoperative elevated blood urea nitrogen (OR 1.4, 95% CI 1.1-1.8; p = 0.014). The ITR-PCVA predictive model was proposed from the resultant multivariable analysis and performed with a modest C-statistic in AUROC analysis of 0.64 (95% CI 0.61-0.66). Multicollinearity diagnostics did not detect any correlation between RAI-rev parameters and other covariates (variance inflation factor = 1). CONCLUSIONS: The current study proposes a novel preoperative risk model for PCVA in patients undergoing ITR. Patients with poor physiological reserve (measured by frailty), multiple comorbidities, abnormal preoperative laboratory values, and those admitted under high acuity were at highest risk. The ITR-PCVA risk model may support patient-centered counseling striving to respect goals of care and maximize quality of life. Future prospective studies are warranted to validate the ITR-PCVA risk model and evaluate its utility as a bedside clinical tool.

Chameleons, red herrings, and false localizing signs in neurocritical care.

False localizing signs (FLS) and other misleading neurological signs have long been an intractable aspect of neurocritical care. Because they suggest an incorrect location or etiology of the pathological lesion, they have often led to misdiagnosis and mismanagement of the patient. Here, we reviewed the existing literature to provide an updated, comprehensive descriptive review of these difficult to diagnose signs in neurocritical care. For each sign presented, we discuss the non-false localizing presentation of symptoms, the common FLS or misleading presentation, etiology/pathogenesis of the sign, and diagnosis, as well as any other clinically relevant considerations. Within cranial neuropathies, we cover cranial nerves III, IV, V, VI, VII, VIII, as well as multiple cranial nerve involvement of IX, X, and XII. FLS ophthalmologic symptoms indicate diagnostically challenging neurological deficits, and here we discuss downbeat nystagmus, ping-pong-gaze, one-and-a-half syndrome, and wall-eyed bilateral nuclear ophthalmoplegia (WEBINO). Cranial herniation syndromes are integral to any discussion of FLS and here we cover Kernohan's notch phenomenon, pseudo-Dandy Walker malformation, and uncal herniation. FLS in the spinal cord have also been relatively well documented, but in addition to compressive lesions, we also discuss newer findings in radiculopathy and disc herniation. Finally, pulmonary syndromes may sometimes be overlooked in discussions of neurological signs but are critically important to recognize and manage in neurocritical care, and here we discuss Cheyne-Stokes respiration, cluster breathing, central neurogenic hyperventilation, ataxic breathing, Ondine's curse, and hypercapnia. Though some of these signs may be rare, the framework for diagnosing and treating them must continue to evolve with our growing understanding of their etiology and varied presentations.

Association of baseline frailty status with clinical outcome following aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent neurosurgical condition associated with high morbidity and mortality. The prognostic significance of baseline frailty status in aSAH patients has not been previously evaluated in a large, nationally representative sample. MATERIALS AND METHODS: Clinical outcomes data from the National Inpatient Sample from 2010-2018 were compared among sub-cohorts stratifying admissions by increasing frailty thresholds [(assessed using the 11-point modified frailty index (mFI-11)]. The previously validated NIS-SAH Severity Score (NIS-SSS) and NIS-SAH Outcome Measure (NIS-SOM) were utilized. Complex samples multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess adjusted associations and discrimination of frailty for endpoints. RESULTS: Among 64,102 aSAH hospitalizations (mean age 55.4 years), 20.4% of admissions were classified as robust (mFI=0), 43.4% as pre-frail (mFI = 1), 24.9% as frail (mFI = 2), and 11.2% as severely frail (mFI ≥ 3). Following multivariable analysis adjusting for age and aSAH severity, increasing frailty was independently associated with NIS-SOM (OR = 1.15, 95% CI 1.09-1.21; p < 0.001), extended length of hospital stay (eLOS) (OR = 1.08, 1.02-1.13; p = 0.008), neurological complications (OR = 1.08, 1.03-1.13; p < 0.001), and medical complications (OR = 1.14, 1.08-1.21; p < 0.001). Based on ROC curve analysis, frailty achieved an AUC of 0.59 (0.58-0.60) and 0.54 (0.53-0.55) for NIS-SOM and eLOS, respectively. Age and NIS-SSS demonstrated significantly greater discrimination for NIS-SOM [AUC 0.69 (0.68-0.70) and 0.79 (0.78-0.80), respectively), while NIS-SSS achieved significantly greater discrimination for eLOS [(AUC 0.74 (0.73-0.75)] in comparison to both age and frailty. CONCLUSIONS: This national database evaluation of frailty in aSAH patients demonstrates an independent association between increasing frailty and poor functional outcome. Age and aSAH severity, however, may be more robust prognostic factors.

Association of baseline frailty status and age with postoperative morbidity and mortality following intracranial meningioma resection.

PURPOSE: Although numerous studies have established advanced patient age as a risk factor for poor outcomes following intracranial meningioma resection, large-scale evaluation of frailty for preoperative risk assessment has yet to be examined. METHODS: Weighted discharge data from the National Inpatient Sample were queried for adult patients undergoing benign intracranial meningioma resection from 2015 to 2018. Complex samples multivariable logistic regression models and receiver operating characteristic curve analysis were performed to evaluate adjusted associations and discrimination of frailty, quantified using the 11-factor modified frailty index (mFI), for clinical endpoints. RESULTS: Among 20,250 patients identified (mean age 60.6 years), 35.4% (n = 7170) were robust (mFI = 0), 34.5% (n = 6985) pre-frail (mFI = 1), 20.1% (n = 4075) frail (mFI = 2), and 10.0% (n = 2020) severely frail (mFI ≥ 3). On univariable analysis, these sub-cohorts stratified by increasing frailty were significantly associated with the development of Clavien-Dindo grade IV (life-threatening) complications (inclusive of those resulting in mortality) (1.3% vs. 3.1% vs. 6.5% vs. 9.4%, p < 0.001) and extended length of stay (eLOS) (15.4% vs. 22.5% vs. 29.3% vs. 37.4%, p < 0.001). Following multivariable analysis, increasing frailty (aOR 1.40, 95% CI 1.17, 1.68, p < 0.001) and age (aOR 1.20, 95% CI 1.05, 1.38, p = 0.009) were both independently associated with development of life-threatening complications or mortality, whereas increasing frailty (aOR 1.20, 95% CI 1.10, 1.32, p < 0.001), but not age, was associated with eLOS. Frailty (by mFI-11) achieved superior discrimination in comparison to age for both endpoints (AUC 0.69 and 0.61, respectively). CONCLUSION: Frailty may be more accurate than advanced patient age alone for prognostication of adverse events and outcomes following intracranial meningioma resection.

The immense heterogeneity of frailty in neurosurgery: a systematic literature review.

The aim of this study was to review and analyze the neurosurgery body of literature to document the current knowledge of frailty within neurosurgery, standardizing terminology and how frailty is defined, including the different levels of frailty, while determining what conclusions can be drawn about frailty's impact on neurosurgical outcomes. While multiple studies on frailty in neurosurgery exist, no literature reviews have been conducted. Therefore, we performed a literature review in order to organize, tabulate, and present findings from the data to broaden the understanding about what we know from frailty and neurosurgery. We performed a PubMed search to identify studies that evaluated frailty and neurosurgery. The terms "frail," "frailty," "neurosurgery," "spine surgery," "craniotomy," and "neurological surgery" were all used in the query. We then organized, analyzed, and summarized the comprehensive frailty and neurosurgical literature. The literature contained 25 published studies analyzing frailty in neurosurgery between December 2015 and December 2018. Five of these studies were cranial neurosurgical studies, the remaining studies focused on spinal neurosurgery. Over 100,000 surgical cases were analyzed among the 25 studies. Of these, 18 studies demonstrated that increasing frailty was associated with increased rate of complications, 10 studies showed that frailty was associated with higher mortality rates, 11 studies demonstrated an association between frailty and increased hospital length of stay, and 5 studies noted that higher frailty was associated with discharge to a higher level of care. The current body of literature repeatedly demonstrates that frailty is associated with worse outcomes across the neurosurgical subspecialties.

A comparison of frailty indices in predicting length of inpatient stay and discharge destination following angiogram-negative subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: While patients with angiogram-negative subarachnoid hemorrhages (ANSAH) have better prognoses than those with aneurysmal SAH, frailty's impact on outcomes in ANSAH is unclear. We previously showed that the modified frailty index (mFI-11) is associated with poor outcomes following ANSAH. Here, we compared the mFI-5, mFI-11, Charlson Comorbidity Index (CCI), and temporalis thickness (TMT) to determine which index was the best predictor of ANSAH outcomes and mortality rates. METHODS: In this retrospective cohort analysis between 2014 and 2018, patients with non-traumatic, angiogram negative SAH (ANSAH) were identified. The admission mFI-5, mFI-11, CCI, and TMT were calculated for each patient. Primary outcomes were mortality rate, discharge location, and prolonged length of stay (PLOS; LOS >85th percentile). Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to evaluate frailty as predictors of primary endpoints. RESULTS: We included 75 patients with a mean age of 55.4 ± 1.5 years. There were 4 patient deaths (5.3%), 53 patients (70.7%) discharged home, and 11 patients (14.7%) with PLOS. On ROC analysis, the mFI-5 had the highest discriminatory value for mortality (AUC = 0.97) while the mFI-11 was most discriminatory for discharge home (AUC = 0.85) and PLOS (AUC = 0.78). On multivariate analysis, the only independent predictor of mortality was the mFI-11 (OR = 0.46; 95%CI: 1.45-14.23; p = 0.009) while the mFI-5 was the best predictor of discharge home (OR = 0.21; 95% CI: 0.08-0.61; p = 0.004). On multivariate analysis, the only independent predictor of PLOS was the Hunt and Hess score (OR = 2.63; 95%CI: 1.38-5.00; p = 0.003). The CCI and TMT were inferior to either mFI for predicting primary endpoints. CONCLUSIONS: Increasing frailty is associated with poorer outcomes and higher mortality following ANSAH. The mFI-5 and mFI-11 were found to be superior predictors of discharge home and mortality rate. While larger prospective study is needed, frailty, as measured by mFI-11 and -5, should be considered when evaluating ANSAH prognosis.

Frailty predicts worse outcomes after intracranial meningioma surgery irrespective of existing prognostic factors.

OBJECTIVE: Frailty has been recognized as a predictor of adverse surgical outcomes across multiple surgical disciplines, but until now the relationship between frailty and intracranial meningioma surgery has not been studied. The goal of the present study was to determine the relationship between increasing frailty (determined using the modified Frailty Index [mFI]) and intracranial meningioma resection outcomes (including hospital length of stay [LOS], discharge location, and reoperation and readmission rates). METHODS: This is a single-center retrospective cohort study of patients who underwent intracranial meningioma resection between August 2012 and May 2018. Seventy-six patients met the inclusion criteria. RESULTS: Frailty was associated with increased hospital LOS (p = 0.0218), increased reoperation rate (p = 0.029), and discharge to a higher level of care: an inpatient rehabilitation facility or a skilled nursing facility (p = 0.0002). After multivariable analysis, frailty was determined to be an independent risk factor for increased LOS, worse discharge disposition, and subsequent readmission. CONCLUSIONS: Frailty is an independent risk factor for worse outcomes following intracranial meningioma resection, including increased LOS, reoperations, and worse discharge disposition. Frailty may help stratify preoperative surgical risk, and thus may provide important clinical information to help neurosurgeons and elderly patients weigh the risks and benefits of resection.

Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-κB pathway inhibition.

BACKGROUND: Traumatic spinal cord injury (SCI) triggers a chain of events that is accompanied by an inflammatory reaction leading to necrotic cell death at the core of the injury site, which is restricted by astrogliosis and apoptotic cell death in the surrounding areas. Activation of nuclear factor-κB (NF-κB) signaling pathway has been shown to be associated with inflammatory response induced by SCI. Here, we elucidate the pattern of activation of NF-κB in the pathology of SCI in rats and investigate the effect of transplantation of spinal neural precursors (SPC-01) on its activity and related astrogliosis. METHODS: Using a rat compression model of SCI, we transplanted SPC-01 cells or injected saline into the lesion 7 days after SCI induction. Paraffin-embedded sections were used to assess p65 NF-κB nuclear translocation at days 1, 3, 7, 10, 14, and 28 and to determine levels of glial scaring, white and gray matter preservation, and cavity size at day 28 after SCI. Additionally, levels of p65 phosphorylated at Serine536 were determined 10, 14, and 28 days after SCI as well as levels of locally secreted TNF-α. RESULTS: We determined a bimodal activation pattern of canonical p65 NF-κB signaling pathway in the pathology of SCI with peaks at 3 and 28 days after injury induction. Transplantation of SCI-01 cells resulted in significant downregulation of TNF-α production at 10 and 14 days after SCI and in strong inhibition of p65 NF-κB activity at 28 days after SCI, mainly in the gray matter. Moreover, reduced formation of glial scar was found in SPC-01-transplanted rats along with enhanced gray matter preservation and reduced cavity size. CONCLUSIONS: The results of this study demonstrate strong immunomodulatory properties of SPC-01 cells based on inhibition of a major signaling pathway. Canonical NF-κB pathway activation underlines much of the immune response after SCI including cytokine, chemokine, and apoptosis-related factor production as well as immune cell activation and infiltration. Reduced inflammation may have led to observed tissue sparing. Additionally, such immune response modulation could have impacted astrocyte activation resulting in a reduced glial scar.

The role of 5-aminolevulinic acid in spinal tumor surgery: a review.

PURPOSE: Primary intradural spinal neoplasms account for a small proportion of central nervous system tumors. The primary treatment for these tumors consists of maximal safe resection and preservation of neurologic function. Gross total resection, which is associated with the lowest rate of tumor recurrence and longer progression-free survival for most histologies, can be difficult to achieve. Currently, the use of 5-aminolevulinc acid (5-ALA) which takes advantage of Protoporphyrin IX (PpIX) fluorescence, is a well-established technique for improving resection of malignant cerebral gliomas. This technique is being increasingly applied to other cerebral neoplasms, and multiple studies have attempted to evaluate the utility of 5-ALA-aided resection of spinal neoplasms. METHODS: The authors reviewed the existing literature on the use of 5-ALA and PpIX fluorescence as an aid to resection of primary and secondary spinal neoplasms by searching the PUBMED and EMBASE database for records up to March 2018. Data was abstracted from all studies describing spinal neurosurgical uses in the English language. RESULTS: In the reviewed studies, the most useful fluorescence was observed in meningiomas, ependymomas, drop metastases from cerebral gliomas, and hemangiopericytomas of the spine, which is consistent with applications in cerebral neoplasms. CONCLUSIONS: The available literature is significantly limited by a lack of standardized methods for measurement and quantification of 5-ALA fluorescence. The results of the reviewed studies should guide future development of rational trial protocols for the use of 5-ALA guided resection in spinal neoplasms.