Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

PURPOSE: The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. METHODS: Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. RESULTS: Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9 ± 18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. CONCLUSIONS: The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.

B-Cell Lymphoma 2 (Bcl-2) and Regulation of Apoptosis after Traumatic Brain Injury: A Clinical Perspective.

Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates the clinical evidence on Bcl-2 and neurological recovery in patients after traumatic brain injury (TBI). Materials and Methods: All studies in English were queried from the National Library of Medicine PubMed database using the following search terms: (B-cell lymphoma 2/Bcl-2/Bcl2) AND (brain injury/head injury/head trauma/traumatic brain injury) AND (human/patient/subject). There were 10 investigations conducted on Bcl-2 and apoptosis in TBI patients, of which 5 analyzed the pericontutional brain tissue obtained from surgical decompression, 4 studied Bcl-2 expression as a biomarker in the cerebrospinal fluid (CSF), and 1 was a prospective randomized trial. Results: Immunohistochemistry (IHC) in 94 adults with severe TBI showed upregulation of Bcl-2 in the pericontusional tissue. Bcl-2 was detected in 36-75% of TBI patients, while it was generally absent in the non-TBI controls, with Bcl-2 expression increased 2.9- to 17-fold in TBI patients. Terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL) positivity for cell death was detected in 33-73% of TBI patients. CSF analysis in 113 TBI subjects (90 adults, 23 pediatric patients) showed upregulation of Bcl-2 that peaked on post-injury day 3 and subsequently declined after day 5. Increased Bcl-2 in the peritraumatic tissue, rising CSF Bcl-2 levels, and the variant allele of rs17759659 are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). Conclusions: Bcl-2 is upregulated in the pericontusional brain and CSF in the acute period after TBI. Bcl-2 has a neuroprotective role as a pro-survival protein in experimental models, and increased expression in patients can contribute to improvement in clinical outcomes. Its utility as a biomarker and therapeutic target to block neuronal apoptosis after TBI warrants further evaluation.

Intermittent versus continuous cerebrospinal fluid drainage management in adult severe traumatic brain injury: assessment of intracranial pressure burden.

INTRODUCTION: There is clinical equipoise regarding whether neurointensive care unit management of external ventricular drains (EVD) in severe traumatic brain injury (TBI) should involve an open EVD, with continuous drainage of cerebrospinal fluid (CSF), versus a closed EVD, with intermittent opening as necessary to drain CSF. In a matched cohort design, we assessed the relative impact of continuous versus intermittent CSF drainage on intracranial pressure in the management of adult severe TBI. METHODS: Sixty-two severe TBI patients were assessed. Thirty-one patients managed by open EVD drainage were matched by age, sex, and injury severity (initial Glasgow Coma Scale (GCS) score) to 31 patients treated with a closed EVD drainage. Patients in the open EVD group also had a parenchymal intracranial pressure (ICP) monitor placed through an adjacent burr hole, allowing real-time recording of ICP. Hourly ICP and other pertinent data, such as length of stay in intensive care unit (LOS-ICU), Injury Severity Score, and survival status, were extracted from our prospective database. RESULTS: With age, injury severity (initial GCS score), and neurosurgical intervention adjusted for, there was a statistically significant difference of 5.66 mmHg in mean ICP (p < 0.0001) between the open and the closed EVD groups, with the closed EVD group exhibiting greater mean ICP. ICP burden (ICP ≥ 20 mmHg) was shown to be significantly higher in the intermittent EVD group (p = 0.0002) in comparison with the continuous EVD group. CONCLUSION: Continuous CSF drainage via an open EVD seemed to be associated with more effective ICP control in the management of adult severe TBI.

Pilot Biomarker Analysis and Decision Tree Algorithm Modeling of Patients with Chronic Subdural Hematomas.

The elderly population are at high risk for developing chronic subdural hematoma (cSDH). Surgical evacuation of cSDH is one of the most common procedures performed in neurosurgery. The present study aims to identify potential inflammatory biomarkers associated with its development and recurrence. Patients (>65 years of age) who presented with symptomatic cSDH (≥1 cm thickness or ≥5 mm midline shift [MLS]), requiring surgical intervention, were prospectively enrolled. The collected cSDH fluid was analyzed for inflammatory markers. Computed tomography (CT) scan data included pre-operative cSDH thickness and MLS. Outcome data included Glasgow Outcome Scale-Extended (GOS-E) score at 3, 6, and 12 months post-surgery, as well as cSDH recurrence. A decision tree model was used to determine the predictive power of extracted analytes for MLS, cSDH thickness, and recurrence. This pilot study includes 20 enrolled patients (mean age 77.9 ± 7.4 years and 85% falls). Rate of cSDH recurrence was 42%, with 21% requiring reoperation. Chemokine (C-X-C motif) ligand 9 (CXCL9) concentrations correlated with cSDH thickness (r = 0.975, p = 0.040). Interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A concentrations correlated with MLS (r = 0.974, p = 0.005; r = 0.472, p = 0.036, respectively). IL-5 concentrations correlated with more favorable GOS-E scores at 3, 6, and 12 months (r = 0.639, p = 0.006; r = 0.727, p = 0.003; r = 0.693, p = 0.026, respectively). Regulated on activation, normal T-cell expressed and secreted (RANTES) concentrations correlated with complete cSDH resolution (r = 0.514, p = 0.021). The decision tree model identified that higher concentrations of CXCL9 were predictive of MLS (risk ratio [RR] = 12.0), higher concentrations of IL-5 were predictive of cSDH thickness (RR = 4.5), and lower concentrations of RANTES were predictive of cSDH recurrence (RR = 2.2). CXCL9, IL-6, VEGF, IL-5, and RANTES are associated with recurrence after surgery and may be potential biomarkers for predicting cSDH recurrence and neurological outcomes.

Long-term Benefits for Younger Patients with Aggressive Immediate Intervention following Severe Traumatic Brain Injury: A Longitudinal Cohort Analysis of 175 Patients from a Prospective Registry.

BACKGROUND: The prevalence of traumatic brain injury (TBI) continues to rise, in part as a reflection of a growing elderly population. Concomitantly, nihilism may exist following substantial neurotrauma from a myriad of commonplace mechanisms, such as traffic incidents, assaults, or falls. OBJECTIVE: This study assesses long-term outcomes following aggressive surgical intervention with invasive neuromonitoring to guard against nihilism, especially for patients with advantageous characteristics such as younger age. METHODS: A consecutive series of patients with severe TBI treated between 2008 and 2018 and enrolled into the Brain Trauma Research Center (BTRC) database, an Institutional Review Board (IRB 19030228) approved prospective, longitudinal cohort study, were extracted. Demographic and clinical data were analyzed. Long-term functional outcome was recorded with the eight-point Glasgow Outcome Scale-Extended (GOS-E) score at 3-, 6-, 12-, and 24-months by trained, qualified neuropsychology technicians. Chi-squared and analysis of variance tests were used to evaluate the relationship of age groups between different variables. RESULTS: For this analysis, 175 patients with severe TBI who were enrolled in the BTRC database and required decompressive hemicraniectomy during the study period were included. Over one-third of the patients with a severe TBI, who were aged 35 years and younger, had a favorable outcome. CONCLUSIONS: Despite enduring a severe TBI, a substantial percentage of younger patients achieved favorable outcomes following aggressive treatment. As such, establishing a prognosis should be deferred to allow for recovery via individualized rehabilitation, multidisciplinary support, and community reintegration programs to cope with various long-term psychological, cognitive, and functional disabilities.

Power Drill Craniostomy for Bedside Intracranial Access in Traumatic Brain Injury Patients.

Invasive neuromonitoring is a bedrock procedure in neurosurgery and neurocritical care. Intracranial hypertension is a recognized emergency that can potentially lead to herniation, ischemia, and neurological decline. Over 50,000 external ventricular drains (EVDs) are performed in the United States annually for traumatic brain injuries (TBI), tumors, cerebrovascular hemorrhaging, and other causes. The technical challenge of a bedside ventriculostomy and/or parenchymal monitor placement may be increased by complex craniofacial trauma or brain swelling, which will decrease the tolerance of brain parenchyma to applied procedural force during a craniostomy. Herein, we report on the implementation and safety of a disposable power drill for bedside neurosurgical practices compared with the manual twist drill that is the current gold standard. Mechanical testing of the drill's stop extension (n = 8) was conducted through a calibrated tensile tester, simulating an axial plunging of 22.68 kilogram (kg) or 50 pounds of force (lbf) and measuring the strength-responsive displacement. The mean displacement following compression was 0.18 ± 0.11 mm (range of 0.03 mm to 0.34 mm). An overall cost analysis was calculated based on the annual institutional pricing, with an estimated $64.90 per unit increase in the cost of the disposable electric drill. Power drill craniostomies were utilized in a total of 34 adult patients, with a median Glasgow Coma Scale (GCS) score of six. Twenty-seven patients were male, with a mean age of 50.7 years old. The two most common injury mechanisms were falls and motor vehicle/motorcycle accidents. EVDs were placed in all subjects, and additional quad-lumen neuromonitoring was applied to 23 patients, with no incidents of plunging events or malfunctions. One patient developed an intracranial infection and another had intraparenchymal tract hemorrhaging. Two illustrative TBI cases with concomitant craniofacial trauma were provided. The disposable power drill was successfully implemented as an option for bedside ventriculostomies and had an acceptable safety profile.

Superiority of craniotomy over supportive care for octogenarians and nonagenarians in operable acute traumatic subdural hematoma.

OBJECTIVE: Neurosurgical evacuation in elderly trauma patients is controversial. We analyzed impact of craniotomy for acute subdural hematoma on survival in octogenarians and nonagenarians. Methods The study population included all patients aged ≥ 80 years who presented with acute traumatic SDHs 09/01/15 - 01/01/20, with radiography indicating operative eligibility (i.e. MLS >5 mm and/or overall thickness >10 mm). Of 1054 TBIs aged ≥ 80 years, 104 (9.87%) were surgically indicated. Of these, 35 received craniotomy and 69 received supportive measures due to family/patient wishes or surgeon's professional decision. We analyzed these data using a Poisson regression adjusted for influence of covariates. RESULTS: Of 35 craniotomies, 21 (60.00%) were deceased at 2 years of follow-up, compared to 48 (69.57%) deceased of 69 non-surgical patients. No significant demographic differences existed between these groups, other than age (craniotomy patients were younger; median age 84 vs 86; p < 0.001). In outcomes, the craniotomy cohort survived longer and in higher proportions (p = 0.028; Gehan-Breslow-Wilcoxon). When adjusting for covariates, this effect became more pronounced: craniotomy patients died at 41.1% the rate of non-surgical ones. Of all the covariates, only initial GCS significantly impacted the protective effect of craniotomy. In a logarithmic relationship, each point on initial GCS was associated with less benefit from surgery. We also found that patients with GCS< 3 were overall less likely to benefit from surgery. Our conclusions are limited by the impact of patient/surgeon choice on whether or not to operate. It is possible healthier subjects elected for craniotomies. We have attempted to correct for this by including comorbidities as covariates in our regression analyses. CONCLUSIONS: Our results indicate a surgical benefit for this elderly cohort, consistent with prior findings of benefit in the setting of severe traumatic aSDH. Patients with worse neurologic impairment, i.e. low GCS, had the greatest survival benefit from surgical intervention.

Time to Follow Commands in Severe Traumatic Brain Injury Survivors With Favorable Recovery at 2 Years.

BACKGROUND: The recovery of severe traumatic brain injury (TBI) survivors with long-term favorable outlook is understudied. Time to follow commands varies widely in this patient population but has important clinical implications. OBJECTIVE: To (1) evaluate time to follow commands in severe patients with TBI with favorable outcomes, (2) characterize their trajectory of recovery, and (3) identify predictors associated with delayed cognitive improvement. METHODS: Participants were recruited prospectively at a Level I trauma center through the Brain Trauma Research Center from 2003 to 2018. Inclusion criteria were age 16 to 80 years, Glasgow Coma Scale score ≤8 and motor score <6, and Glasgow Outcome Scale-Extended measure ≥4 at 2 years postinjury. RESULTS: In 580 patients, there were 229 (39.5%) deaths and 140 (24.1%) patients had favorable outcomes at 2 years. The mean age was 33.7 ± 14.5 years, median Glasgow Coma Scale was 7 (IQR 6-7), and median Injury Severity Score was 30 (IQR 26-38). The mean time to follow commands was 12.7 ± 11.8 days. On multivariable linear regression, the presence of diffuse axonal injury (B = 9.2 days [4.8, 13.7], P < .0001) or intraventricular hemorrhage (B = 6.4 days [0.5, 12.3], P < .035) was associated with longer time before following commands and patients who developed nosocomial infections (B = 6.5 days [1.6-11.4], P < .01). CONCLUSION: In severe TBI survivors with favorable outcomes, time to follow commands varied widely. Most patients began to follow commands within 2 weeks. Evidence of diffuse axonal injury, intraventricular hemorrhage, and infections can delay cognitive improvement in the acute period. Patients make considerable recovery up to 2 years after their injury.

Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium.

Drug repurposing has the potential to bring existing de-risked drugs for effective intervention in an ongoing pandemic-COVID-19 that has infected over 131 million, with 2.8 million people succumbing to the illness globally (as of April 04, 2021). We have used a novel `gene signature'-based drug repositioning strategy by applying widely accepted gene ranking algorithms to prioritize the FDA approved or under trial drugs. We mined publically available RNA sequencing (RNA-Seq) data using CLC Genomics Workbench 20 (QIAGEN) and identified 283 differentially expressed genes (FDR<0.05, log2FC>1) after a meta-analysis of three independent studies which were based on severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in primary human airway epithelial cells. Ingenuity Pathway Analysis (IPA) revealed that SARS-CoV-2 activated key canonical pathways and gene networks that intricately regulate general anti-viral as well as specific inflammatory pathways. Drug database, extracted from the Metacore and IPA, identified 15 drug targets (with information on COVID-19 pathogenesis) with 46 existing drugs as potential-novel candidates for repurposing for COVID-19 treatment. We found 35 novel drugs that inhibit targets (ALPL, CXCL8, and IL6) already in clinical trials for COVID-19. Also, we found 6 existing drugs against 4 potential anti-COVID-19 targets (CCL20, CSF3, CXCL1, CXCL10) that might have novel anti-COVID-19 indications. Finally, these drug targets were computationally prioritized based on gene ranking algorithms, which revealed CXCL10 as the common and strongest candidate with 2 existing drugs. Furthermore, the list of 283 SARS-CoV-2-associated proteins could be valuable not only as anti-COVID-19 targets but also useful for COVID-19 biomarker development.

Evaluation of free-hand screw placement in cervical, thoracic, and lumbar spine by neurosurgical residents.

BACKGROUND: Knowledge of free-hand screw technique remains critical to adequately train neurosurgical residents. The purpose of this study was to evaluate the accuracy of screw placement via the free-hand technique in lumbar, thoracic, and cervical spine by neurosurgical residents completing an enfolded spine fellowship. METHODS: Medical records of all patients who underwent free-hand screw placement at all spinal levels over a 6-month period by senior neurosurgical residents enrolled in an in-folded spine fellowship were retrospectively reviewed. Postoperative CT images were assessed for presence and direction of cortical breach. RESULTS: Twenty-six patients underwent 162 free-hand screw placements. The most commonly placed screws were cervical lateral mass screws (n = 69), thoracic (n = 41), and lumbar pedicle screws (n = 41). The most common indication for surgery was deformity (n = 22), followed by infection (n = 2) and trauma (n = 2). Fifty-five breaches were identified in 44 (27 %) screws placed in 21 patients (81 %). Anterior breach was identified in 22 cases (40.0 %), lateral in 12 (23.6 %), superior in 7 (12.7 %), and inferior in 7 (12.7 %), and medial in 6 (10.9 %). The most common level of breach was observed in cervical lateral mass screws (n = 19, 43 %) and least common in C2 pars screws (n = 1, 2%). With an average length of follow up of 12.1 ± 7.7 months of follow-up, no clinical sequalae of screw breach was observed. CONCLUSIONS: Despite the high prevalence of screw breach using the free-hand technique by neurosurgical residents, the absence of clinical sequelae implies safety and emphasizes the importance of early exposure to this technique during neurosurgical residency training.

Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury.

Traumatic brain injury (TBI) induces a pathophysiologic state that can be worsened by secondary injury. Monitoring brain metabolism with intracranial microdialysis can provide clinical insights to limit secondary injury in the days following TBI. Recent enhancements to microdialysis include the implementation of continuously operating electrochemical biosensors for monitoring the dialysate sample stream in real time and dexamethasone retrodialysis to mitigate the tissue response to probe insertion. Dexamethasone-enhanced continuous-online microdialysis (Dex-enhanced coMD) records long-lasting declines of glucose after controlled cortical impact in rats and TBI in patients. The present study employed retrodialysis and fluorescence microscopy to investigate the mechanism responsible for the decline of dialysate glucose after injury of the rat cortex. Findings confirm the long-term functionality of Dex-enhanced coMD for monitoring brain glucose after injury, demonstrate that intracranial glucose microdialysis is coupled to glucose utilization in the tissues surrounding the probes, and validate the conclusion that aberrant glucose utilization drives the postinjury glucose decline.

B-Cell Lymphoma 2 (Bcl-2) Gene Is Associated with Intracranial Hypertension after Severe Traumatic Brain Injury.

Severe traumatic brain injury (TBI) activates the apoptotic cascade in neurons and glia as part of secondary cellular injury. B-cell lymphoma 2 (Bcl-2) gene encodes a pro-survival protein to suppress programmed cell death, and variation in this gene has potential to affect intracranial pressure (ICP). Participants were recruited from a single clinical center using a prospective observational study design. Inclusion criteria were: age 16-80 years; Glasgow Coma Scale (GCS) score 4-8; and at least 24 h of ICP monitoring treated between 2000-2014. Outcomes were mean ICP, spikes >20 and >25 mm Hg, edema, and surgical intervention. Odds ratios (OR), mean increases/decreases (B), and 95% confidence intervals (CIs) were reported. In 264 patients, average age was 39.2 years old and 78% of patients were male. Mean ICPs were 11.4 ± 0.4 mm Hg for patients with homozygous wild-type (AA), 12.8 ± 0.6 mm Hg for heterozygous (AG), and 14.3 ± 1.2 mm Hg for homozygous variant (GG; p = 0.023). Rs17759659 GG genotype was associated with more ICP spikes >20 mm Hg (p = 0.017) and >25 mm Hg (p = 0.048). Multi-variate analysis showed that GG relative to AA genotype had higher ICP (B = 2.7 mm Hg, 95% CI [0.5,4.9], p = 0.015), edema (OR = 2.5 [1.0, 6.0], p = 0.049) and need for decompression (OR = 3.7 [1.5-9.3], p = 0.004). In this prospective severe TBI cohort, Bcl-2 rs17759659 was associated with increased risk of intracranial hypertension, cerebral edema, and need for surgical intervention. The variant allele may impact programmed cell death of injured neurons, resulting in elevated ICP and post-traumatic secondary insults. Further risk stratification and targeted genotype-based therapies could improve outcomes after severe TBI.

Causes of hospital readmissions within 7 days from the neurosurgical service of a quaternary referral hospital.

BACKGROUND: Evaluation of readmission rates as a proxy metric of health-care quality in neurological surgery has grown to become a prevalent area of investigation in the last several years. Significant attention has been paid to 30-day readmission rates due to the financial incentive to health-care providers following the enforcement of the penalties created by the Affordable Care Act. However, relatively little attention has been paid to patients readmitted within 7 days of discharge to large quaternary neurological surgery services. This study was conducted to examine the causes and unique characteristics of 7-day readmission rates from a neurosurgical service at a large quaternary referral hospital. METHODS: A retrospective observational analysis of all 7-day readmissions to the neurosurgical surgery service of the University of Pittsburgh Medical Center, Presbyterian Hospital from August 2017 to June 2019, was performed. Patients were organized into seven categories based on their primary reason for readmission: scheduled surgeries, infection, pain, altered mental status or seizures, general postoperative complications, complications directly resulting from a neurosurgical intervention, and unrelated reasons. Demographic information, the time between initial discharge and subsequent readmission, and discharge disposition were also recorded. RESULTS: Of 5274 discharges, 258 patients (4.9%) were readmitted within 7 days (55.0% male; mean age 60 years of age). Two-thirds of patients readmitted initially underwent care for cranial pathologies (57% of 258 patients) as opposed to a third for spine pathologies (33% of 258 patients). Complications that directly arose from the neurosurgical intervention (e.g., shunt infection or misplacement, and hardware misplacement) represented 18.9% of total readmission, while general postoperative complications (e.g., urinary tract infection) accounted for 15.1% of total readmission, in which all together were slightly greater than a third of readmissions. Seizures or altered mental status led to less than a fifth of readmissions (17.0%), followed by readmissions from unrelated diagnosis or miscellaneous reasons (17.0%) and scheduled surgeries (13.1%). Taken together, surgical site infections (9.7%) and postoperative pain (9.3%) accounted for 9.7% and 9.3 % of readmissions, respectively. CONCLUSION: Approximately 5% of patients discharged in a single year from our quaternary referral center were readmitted within 7-days. Approximately 90% of all 7-day readmissions were unplanned, with one-third resulting directly from perioperative complications. Further investigation to better understand this acutely vulnerable yet previously overlooked population may guide focused efforts to increase the quality of neurosurgical patient care.

Perioperative Neurological Complications Following Anterior Cervical Discectomy and Fusion: Clinical Impact on 317,789 Patients from the National Inpatient Sample.

BACKGROUND: Perioperative neurologic complication after an anterior cervical discectomy and fusion (ACDF) is uncommon but may have significant clinical consequences. OBJECTIVE: We aim to estimate the incidence of perioperative neurologic complications, identify their risk factors, and evaluate their impact on morbidity and mortality after ACDF. METHODS: ACDF cases (n = 317,789 patients) were extracted from the National Inpatient Sample between 1999 and 2011. Based on their Elixhauser-van Walraven score (VWR), patients were classified as low (VWR < 5), moderate (5-14), or high risk (>14) for surgery. The primary outcome was perioperative neurologic complications. Secondary outcomes included morbidity (hospital length of stay >14 days or discharge disposition to a location other than home) and in-hospital mortality. RESULTS: The rate of perioperative neurologic complications, morbidity, and mortality after ACDF was 0.4%, 8.4%, and 0.1%, respectively. Perioperative neurologic complications were highly associated with in-house morbidity (odds ratio [OR], 3.7 [3.1-4.4]) and mortality (OR, 8.0 [4.1-15.5]). The strongest predictors for perioperative neurologic complications were moderate- (OR, 3.1 [2.6-3.7]) and high-risk VWR (OR, 5.4 [3.3-8.9]), postoperative hematoma/seroma formation (OR, 5.4 [3.9-7.4]), and obesity (OR, 1.9 [1.6-2.3]). The rate of perioperative neurologic complications increased from 0.2% to 0.7% from 1999 to 2011, which was temporally associated with the rise in moderate- (P = 0.002) and high-risk patients (P = 0.001) undergoing ACDF. CONCLUSIONS: Perioperative neurologic complications are independent predictors of in-hospital morbidity and mortality after ACDF. Both morbidity and perioperative neurologic complications have increased between 1999 and 2011, which may be due, in part, to increasing numbers of moderate- and high-risk patients undergoing ACDF.

Impact of Perioperative Neurologic Deficits on Clinical Outcomes After Posterior Cervical Fusion.

BACKGROUND: In the United States, the number of posterior cervical fusions has increased substantially. Perioperative neurologic complications associated with this procedure, such as spinal cord and peripheral nerve injuries, can have significant effects on patient health. We examined the impact of perioperative neurologic deficits on mortality in patients undergoing posterior cervical fusion. The secondary aim was to understand the risk factors for perioperative neurologic complications. METHODS: Data were collected from the National Inpatient Sample (NIS) Health Cost Utilization Project (HCUP) between 1999 and 2011. Patients younger than 18 years and older than 80 years were excluded, as were patients who underwent posterior cervical fusion caused by trauma. Patient demographics and comorbidities were compiled as well as variables that have been associated with increased risk of perioperative neurologic deficits. We used the van Walraven score, a weighted numeric surrogate for the Elixhauser comorbidity index, as a covariate to assess comorbidities that have been associated with in-hospital mortality and morbidity after posterior cervical fusion. In addition, we performed univariate comparisons between covariates and surgical outcomes. We conducted a multivariable logistic regression, adjusting for many of the covariates, as well as trend analyses. RESULTS: An analysis of 33,644 patients yielded an overall rate of perioperative neurologic deficits, morbidity, and mortality of 1.08%, 40.44%, and 1.00%, respectively. Perioperative neurologic deficits were independent risk factors predictors of in-hospital mortality (odds ratio, 5.270; P < 0.0001) and morbidity (odds ratio, 2.579; P < 0.0001). Other statistically significant predictors of mortality included increasing van Walraven score, myocardial infarction, metastatic cancer, and weight loss. These were also independent predictors of morbidity along with but not limited to age, device complications, congestive heart failure, paralysis, diabetes with chronic complications, deficiency anemias, device complications, and intraspinal abscess. CONCLUSIONS: Perioperative neurologic deficits are serious complications of posterior cervical fusion and can independently predict in-hospital mortality and morbidity. As this procedure continues to be used increasingly, attention should be directed toward preventing these complications and intervening earlier in patients who have a neurologic deficit. Future efforts should be geared toward screening for at-risk patients with the initiation of surgical prehabilitation.

Risk factors and clinical impact of perioperative neurological deficits following thoracolumbar arthrodesis.

OBJECTIVES: The rates of arthrodesis performed in the United States and globally have increased tremendously in the last 10-15 years. Amongst the most devastating complications are neurological deficits including spinal cord injury, nerve root irritation, and cauda equine syndrome. The primary purpose of this study is to understand the risk factors for perioperative neurological deficits in patients undergoing thoracolumbar fusion. PATIENTS AND METHODS: Data from the Nationwide Inpatient Sample between the years of 1999-2011 was analyzed. Patients were between the ages of 18 and 80 who had thoracolumbar fusion. Excluded were patients who underwent the procedure as a result of trauma or a malignancy. A list of covariates, including demographic variables, preoperative and postoperative variables that are known to increase the risk of perioperative neurological deficits were compiled. Statistical analysis utilized univariate and multivariate logistic regression for comparisons between these covariates and the proposed outcomes. RESULTS: The analysis of 37,899 patients yielded an overall rate of perioperative neurological deficits and mortality of 1.20% and 0.27%, respectively. Risk factors for perioperative neurological deficits included increasing age (OR 1.023 95% CI 1.018-1.029), Van Walraven 5-14 (OR 1.535 95% CI 1.054-2.235), and preoperative paralysis (OR 2.551 95% CI 1.674-3.886). Furthermore, the data showed that being 65 years old or older doubled the risk for perioperative deficit (OR 1.655, CI 1.248-2.194, p < 0.001). CONCLUSIONS: This population based study found that increasing age, higher comorbid burden, and preoperative paralysis increased the risk of perioperative neurological deficits while female gender and hypertension were found to be protective.

Time course of cerebrospinal fluid inflammatory biomarkers and relationship to 6-month neurologic outcome in adult severe traumatic brain injury.

OBJECTIVE: Activation of the inflammatory cascade is a known pathophysiologic process in severe traumatic brain injury (TBI) with yet non-standardized scientific data regarding relationship to outcome. The understanding of the time course of expression of cerebrospinal fluid (CSF) biomarker levels following severe TBI is an important step toward using these biomarkers to measure injury severity and/or early response to therapeutic interventions. The objective of the current study is to report the time course and values of a battery of CSF inflammatory biomarkers following severe TBI in our reasonably sized patient cohort. PATIENTS AND METHODS: Our patient cohort consists of 32 consented patients, who met the study's inclusion criteria for data collection from 2000 to 2010. The time course and values of a battery of CSF biomarkers (IL-1ß, IL-6, TNF-α, IFN-γ, IL-12p70, IL-10, and IL-8) following severe TBI in this patient cohort was characterized. Additionally, the correlation of biomarker concentration with 6-month neurological outcome was assessed. Serial CSF sampling through an external ventricular drain was performed over the first five days following injury. Concentration of a panel of inflammatory biomarkers (IL-1ß, IL-6, TNF-α, IFN-γ, IL-12p70, IL-10, and IL-8) were evaluated using Meso Scale Discovery's Multi-Array technology. Glasgow Outcome Scale (GOS) score at six months following injury was dichotomized into poor outcome (GOS 1-3) and favorable outcome (GOS 4-5). Statistical analyses were performed using Kruskal-Wallis test and linear regression analysis. RESULTS: The result shows that CSF concentrations of inflammatory biomarkers had a significant association with 6-month neurological outcome (p-values≤0.05 for each marker), with the favorable outcome group having lower concentrations of these biomarkers on average, in comparison to the poor neurologic outcome group over the first five days after TBI. All inflammatory biomarkers decreased to normal levels by post-trauma day 5, except for IL-6 and IL-8. Upregulation and increased expression of key inflammatory markers following severe TBI were significant predictors of worse 6-month neurologic outcome. Additionally, post-trauma day 5 concentrations of IL-6 and IL-8 remained elevated over normal CSF values. CONCLUSION: The study shows that inflammatory biomarkers in CSF are potential biomarkers of injury severity and progression and/or recovery; they could prove beneficial in the future assessment of injury severity and response to therapy after severe TBI.

Diagnostic value of somatosensory evoked potential changes during carotid endarterectomy: a systematic review and meta-analysis.

IMPORTANCE: Perioperative stroke is a persistent complication of carotid endarterectomy (CEA) for patients with symptomatic carotid stenosis (CS). OBJECTIVE: To evaluate whether changes in somatosensory evoked potential (SSEP) during CEA are diagnostic of perioperative stroke in patients with symptomatic CS. DESIGN, SETTING, AND PARTICIPANTS: We searched PubMed and the World Science Database for reference lists of retrieved studies and/or experiments on SSEP use in postoperative outcomes following CEA in patients with symptomatic CS from January 1, 1950, through January 1, 2013. We independently screened all titles and abstracts to identify studies that met the inclusion criteria and extracted relevant articles in a uniform manner. Inclusion criteria included randomized clinical trials, prospective studies, or retrospective cohort reviews; population of symptomatic CS; use of intraoperative SSEP monitoring during CEA; immediate postoperative assessment and/or as long as a 3-month follow-up; a total sample size of 50 or more patients; studies with adult humans 18 years or older; and studies published in English. MAIN OUTCOME AND MEASURE: Whether intraoperative SSEP changes were diagnostic of perioperative stroke indicated by postoperative neurological examination. RESULTS: Four-hundred sixty-four articles were retrieved, and 15 prospective and retrospective cohort studies were included in the data analysis. A 4557-patient cohort composed the total sample population for all the studies, 3899 of whom had symptomatic CS. A change in SSEP exhibited a strong pooled mean specificity of 91% (95% CI, 86-94) but a weaker pooled mean sensitivity of 58% (95% CI, 49-68). A pooled diagnostic odds ratio for individual studies of patients with neurological deficit with changes in SSEPs was 14.39 (95% CI, 8.34-24.82), indicating that the odds of observing an SSEP change among those with neurologic deficits were 14 times higher than in individuals without neurologic deficit. CONCLUSIONS AND RELEVANCE: Intraoperative SSEP is a highly specific test in predicting neurological outcome following CEA. Patients with perioperative neurological deficits are 14 times more likely to have had changes in SSEPs during the procedure. The use of SSEPs to design prevention strategies is valuable in reducing perioperative cerebral infarctions during CEA.