Effect of perioperative anticoagulant prophylaxis in patients with traumatic subdural hematoma and a history of anticoagulant use: a propensity-matched National Trauma Data Bank analysis.

OBJECTIVE: The use of anticoagulation to prevent venous thromboembolism (VTE) is controversial in the setting of neurosurgical decompression for traumatic subdural hematoma (SDH). In these patients, there is concern that anticoagulation may cause secondary hemorrhage, increasing the risk of death and other complications. Patients with a history of anticoagulant use are at further risk of VTE, but the effect of VTE prophylaxis (VTEP) following neurosurgery for SDH has not been thoroughly investigated in this population. This study aims to investigate the differences in in-hospital outcomes in patients with SDH and preexisting anticoagulant use who received VTEP following neurosurgical intervention compared with those who did not. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all patients with preexisting anticoagulant use presenting with an SDH who subsequently underwent neurosurgical intervention. Patients who received VTEP were propensity score matched with patients who did not based on demographics, insurance type, injury severity, and comorbidities. Paired Student t-tests, Pearson's chi-square tests, and Benjamini-Hochberg multiple comparisons correction were used to compare differences in in-hospital complications, length of stay (LOS), and mortality rate between the two groups. A logistic regression model was developed to identify risk factors for in-hospital mortality. RESULTS: Two thousand seven hundred ninety-four patients matching the inclusion criteria were identified, of whom 950 received VTEP. Following one-to-one matching and multiple comparisons correction, the VTEP group had a lower mortality rate (18.53% vs 34.53%, p < 0.001) but longer LOS (14.09 vs 8.57 days, p < 0.001) and higher rates of pressure ulcers (2.11% vs 0.53%, p = 0.01), unplanned intensive care unit admission (9.05% vs 3.47%, p < 0.001), and unplanned intubation (9.47% vs 6.11%, p = 0.021). The multivariable logistic regression showed that use of unfractionated heparin (UH; OR 0.36, p < 0.001) and low-molecular-weight heparin (LMWH; OR 0.3, p < 0.001) were associated with lower odds of in-hospital mortality. CONCLUSIONS: In patients with traumatic SDH and a history of anticoagulant use, perioperative VTEP was associated with increased LOS but provided a mortality benefit. LMWH and UH use were the strongest predictors of survival.

Racial disparities in incidence, treatment, and survival in adult brain metastases: a 10-year national database analysis.

OBJECTIVE: The aim of this study was to assess demographic and racial disparities in incidence, treatment, and survival of adults with metastatic malignancy to the brain. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) Program database, the authors identified adults with nonprimary brain metastases between 2010 and 2019. Incidence was calculated for all 10 years while data from 2010 to 2014 were used for survival analysis. The primary outcome measure was all-cause mortality within 5 years, assessed by 6-month, 1-year, 2-year, and 5-year survival rates. Chi-square tests of independence and one-way ANOVA were used to compare categorical and continuous measures, respectively, between non-Hispanic White (NHW), Hispanic White (HW), Black, and Asian/Pacific Islander (API) patients. A multivariable Cox proportional hazards model was developed to evaluate the risk of death within 5 years. RESULTS: A total of 64,690 patient records were identified and analyzed following exclusion based on age (patients > 84 years or < 18 years were excluded), missing race data, and missing survival data. Incidences are reported per 100,000 adults. The incidence of brain metastases increased from 2.59 in 2010 to 2.78 in 2019, with an average 10-year incidence of 2.72. API patients had the highest population-adjusted incidence (3.52), followed by NHW (2.99), Black (2.32), and HW (1.59) patients. Black patients were the most likely to have low income and single status, while API patients were the most likely to have high income and married status. Subsequently, Black patients had the shortest survival time (9.05 months vs 9.19 months for NHW vs 12.93 months for HW vs 15.89 months for API patients, p < 0.001). After controlling for the effect of socioeconomic factors on survival, the multivariable analysis showed that Black (HR 0.91, 95% CI 0.88-0.94), HW (HR 0.73, 95% CI 0.69-0.76), and API (HR 0.69, 95% CI 0.66-0.73) patients all had a survival advantage compared with NHW patients. Surgery also conferred a strong survival advantage (HR 0.47, 95% CI 0.44-0.49). CONCLUSIONS: The incidence of brain metastases has increased slightly between 2010 and 2019, with the highest rate in API patients. Black patients had the lowest survival, potentially due to poor socioeconomic status and lower rates of surgery and chemotherapy. Black patients were the most likely to not be recommended surgery, suggesting a discrepancy in services offered to these patients. More research is warranted to understand the underlying causes of these disparities.

Characteristics of work-related spine injury in the USA: a National Trauma Data Bank analysis.

PURPOSE: Workplace injury is a commonplace occurrence in the USA. Spine injuries are especially devastating as they can cause chronic pain and limit mobility which prevents patients from returning to work. Gaining a better understanding of the patients, mechanisms, and treatments associated with these injuries can aid in improving outcomes. The purpose of this study is to characterize the nature of work-related spine injuries. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all diagnoses involving the cervical, thoracic, lumbar, and sacral spine. Patient demographics, comorbidities, injury characteristics, spinal diagnoses, and procedures were identified for each occupation. Occupational industries, patient demographics, mechanisms of injury, diagnoses, and spinal procedures were characterized. RESULTS: A total of 100,842 work-related injuries were identified between 2017 and 2019. Of those, 19,002 (19%) were spine injuries, and subsequently, 3963 (21%) required spinal surgery. Eight thousand twenty-nine (42%) cases were seen among construction workers, which had the highest proportion of Hispanic patients (36%). Smoking was prevalent in labor-intensive occupations with high rates of spine injury such as building and grounds maintenance. The most common mechanism of injury was a fall from a roof. The most common injury diagnoses were L1, L2, and L3 fractures, and the most common procedures were T12-L1 fusion, multilevel thoracic fusion, and multilevel lumbar fusion. CONCLUSION: Spine injuries represent a significant portion of work-related injuries in the USA and a considerable portion require neurosurgical intervention. Initial efforts should focus on the prevention and management of lumbar spine injuries in the construction industry.

Outcomes of patients undergoing single-level arthroplasty versus anterior lumbar interbody fusion.

BACKGROUND: Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. METHODS: An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. RESULTS: Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30 days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). CONCLUSIONS: ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.

The role of bone mineral density in adult spinal deformity patients undergoing corrective surgery: a matched analysis.

STUDY DESIGN: Retrospective cohort. BACKGROUND: Over 44 million adults are estimated to have either osteoporosis or osteopenia. Adult spinal deformity (ASD) is estimated to affect between 32 and 68% of the elderly population. OBJECTIVE: Retrospective investigation comparing rates of postoperative complications following thoracolumbar scoliosis surgery in patients with normal bone mineral density (BMD) to those with osteopenia or osteoporosis in addition to analyzing the effects of pretreatment with anti-osteoporotic medications in patients with low BMD. METHODS: Using administrative database of Humana beneficiaries, ICD-9 and ICD-10 diagnosis codes were used to identify ASD patients undergoing multilevel thoracolumbar fusions between 2007 and 2017. RESULTS: The propensity matched population analyzed in this study contained 1044 patients equally represented by those with a history of osteopenia, osteoporosis, or normal BMD. Osteopenia and osteoporosis were associated with increased odds of revision surgery (OR 2.01 95% CI 1.36-2.96 and OR 1.57, 95% CI 1.05-2.35), respectively. Similarly, there was an almost twofold increased odds of proximal and distal junctional kyphosis in patients with osteopenia and osteoporosis (OR 1.95, 95% CI 1.40-2.74 and OR 1.88, 95% CI 1.34-2.64), respectively. A total of 258 (37.1%) patients with osteoporosis were pretreated with anti-osteoporotic medications and there was no statistically significant decrease in odds of proximal or distal junctional kyphosis or revision surgery in these patients. CONCLUSION: Patients with ASD undergoing multilevel thoracolumbar fusion surgery have significantly higher rates of postoperative pseudarthrosis, proximal and distal junctional kyphosis, and revision surgery rates compared to patients with normal BMD.

Pediatric primary high-grade spinal glioma: a National Cancer Database analysis of current patterns in treatment and outcomes.

PURPOSE: Pediatric primary high-grade spinal glioma (p-HGSG) is an extremely rare disease process, with little data within the current literature. Akin to primary high-grade gliomas, this cancer has been exemplified by dismal prognosis and poor response to modern treatment paradigms. This study seeks to investigate the current trends affecting overall survival using the National Cancer Database (NCDB). METHODS: The NCDB was queried for p-HGSG between 2004 and 2016, by utilizing the designated diagnosis codes. Kaplan-Meier curves were generated, and log-rank testing was performed to analyze factors affecting overall survival. In addition, a Cox proportional-hazards model was used to perform multivariate regression analysis of survival outcomes. RESULTS: A cohort of 97 patients was identified with a histologically confirmed p-HGSG. The overall incidence of p-HGSG in all pediatric spinal cord tumors is 7.5%, with a mean survival time of 25.3 months (SD, 21.0) and 5-year overall survival of 17.0%. The majority of patients underwent surgery (n = 87, 89.7%), radiotherapy (n = 73, 75.3%), and chemotherapy (n = 60, 61.9%). Univariate, multivariate, and Kaplan-Meier log-rank testing failed to demonstrate an association between performing surgery, extent of resection, radiotherapy, or chemotherapy with improved survival outcomes. CONCLUSIONS: The current study constitutes the largest retrospective analysis of p-HGSGs to date, finding that current treatment options of surgery, radiotherapy, and chemotherapy have unclear benefit. This disease process has a poor prognosis without a current modality of treatment that conclusively alters survival. The risks and side effects of these treatment modalities must be carefully considered in such a highly aggressive disease process, especially given potentially limited survival benefits.

Adult primary high-grade spinal glioma: a nationwide analysis of current trends in treatment and outcomes.

PURPOSE: High-grade spinal glioma (HGSG) is an extremely rare, malignant neoplasm insufficiently described in the literature. We sought to investigate the effect of epidemiological risk factors and treatment strategies on the prognosis of HGSGs using the National Cancer Database (NCDB). METHODS: Patients with diagnosis codes specific for HGSG were queried from the NCDB during the years 2004-2016. Kaplan-Meier curves were generated with log-rank testing performed to assess factors affecting survival. Univariate and multivariate Cox regression analysis was also performed to investigate overall survival. RESULTS: 396 patients were identified with a histologically-confirmed diagnosis of HGSG between 2004-2016. The mean survival time for all patients was 24.5 months (SD: 20.3). Multivariate Cox proportional-hazards regression analysis revealed that tumor size of 26-50 mm (HR 4.96, 95% CI 1.76-13.98, p < 0.01) and greater than 50 mm (HR 4.67, 95% CI 1.43-15.23, p = 0.01) were associated with worsened overall survival in comparison to lesions less than 26 mm. While quality of life was not investigated, both Kaplan-Meier log-rank testing and regression analysis failed to demonstrate an association of survival outcomes with extent of resection, radiotherapy, or chemotherapy. CONCLUSION: The current study represents the largest retrospective analysis of adult primary high-grade spinal glioma to date. Our analysis found no relationship between the extent of surgical resection and survival outcomes. In addition, we failed to show any statistically significant survival benefit with radiotherapy or chemotherapy. This disease process has a poor prognosis without a current modality of treatment that improves survival.

Pituitary germinomas: a multi-institutional study analyzing patient demographics and management patterns.

PURPOSE: Intracranial germinomas are exceedingly rare tumors found in the pineal and suprasellar regions. The extremely low incidence of pituitary germinoma has resulted in a significant gap in knowledge regarding its demographics, management, and treatment outcomes. We present the largest multicenter analysis of pituitary germinomas to date, focused on analyzing demographic and management patterns. METHODS: This study utilizes the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (2004-2016) to study patients with a primary intracranial germinoma of the pituitary gland. We analyzed demographic information and management strategies among adult and pediatric populations and conducted a 20-year overall survival analysis using Kaplan-Meier curve for a descriptive evaluation of survival outcomes between age groups and treatment groups. RESULTS: 92 patients were included in the study, consisting of 58% pediatric patients and 42% adults, with overall 60% males. 82% patients received radiation as part of the treatment, with no significant difference between pediatric and adult groups. Chemotherapy was used significantly more in pediatrics (p = 0.0002) while surgery was significantly more common in adults (p = 0.0117). The most common treatment in pediatrics was radiation + chemotherapy (47%), while the most common treatment in adults was radiation + gross total resection + chemotherapy (23%) followed by radiation + gross total resection (19%). Younger age, radiotherapy, and chemotherapy were associated with increased 20-year survival on Kaplan-Meier curves. CONCLUSIONS: There exist significant differences in the management of pediatric and adult populations with pituitary germinomas. The low incidence of these tumors makes them challenging to study, but also highlights the importance of national cancer registries in amassing sufficient patient data from which to draw evidence-based conclusions.

Gunshot wounds to the head: racial disparities in inpatient management and outcomes.

OBJECTIVE: Several studies have indicated that racial disparities may exist in the management and outcomes of acute trauma care. One segment of trauma care that has not been as extensively investigated, however, is that of cranial trauma care. The goal of this study was to determine whether significant differences exist among racial and ethnic groups in various measures of inpatient management and outcomes after gunshot wounds to the head (GWH). METHODS: In this study, the authors used the Nationwide (National) Inpatient Sample (NIS) to investigate all-cause mortality, receipt of surgery, days from admission to initial intervention, discharge disposition, length of hospital stay, and total hospital charges of those with GWH from 2012 to 2016. A 1:1 propensity score-matched analysis was conducted to evaluate the effect of race on these endpoints, while controlling for baseline demographics and comorbidities. RESULTS: A total of 333 patients met the inclusion and exclusion criteria: 148 (44.44%) white/Caucasian, 123 (36.94%) black/African American, 54 (16.22%) Hispanic/Latinx, and 8 (2.40%) Asian. African American patients were sent to immediate care and rehabilitation significantly less often than Caucasian patients (RR 0.17 [95% CI 0.04-0.71]). There were no significant differences in mortality, length of stay, rates of surgical intervention, or total hospital charges among any of the racial groups. CONCLUSIONS: The authors' findings suggest that racial disparities in inpatient cranial trauma care and outcomes may not be as prevalent as previously thought. In fact, the disparities seen were only in disposition. More research is needed to further elucidate and address disparities within this population, particularly those that may exist prior to, and after, hospitalization.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Mycobacterium fortuitum Meningitis: Approach to Lumboperitoneal Shunt Infection.

Mycobacterium fortuitum is a rare, opportunistic pathogen most frequently contracted through contact with a contaminated source. An immunocompetent 26-year-old female patient presented to our institution with an infected lumboperitoneal (LP) shunt presenting as continued nonhealing wounds. After multiple debridements, shunt revisions, and wound closure failures, infectious disease specialists were consulted. The wound cultures returned positive for M. fortuitum and the shunt was removed. Cerebrospinal fluid studies revealed significant pleocytosis with normal opening pressure, and the patient was diagnosed as having secondary meningitis. After shunt removal, the patient was treated with intravenous and oral antibiotics, resulting in infection resolution. Five months later, a new LP shunt was placed without infection recurrence. Although M. fortuitum was previously reported in neurosurgical patients with ventriculoperitoneal shunts, which are summarized here, to date this is the first case in the literature of M. fortuitum meningitis from an LP shunt. This case demonstrates the importance of clinicians considering uncommon and slow-growing pathogens, as well as consulting infectious disease specialists for patients with persistent, unexplained infections.

Localized targeted antiangiogenic drug delivery for glioblastoma.

Systemic delivery of antiangiogenic agents has been ineffective in improving the overall survival of patients with both primary and recurrent glioblastoma, in part due to dose-limiting toxicities. With the development of new and efficient localized delivery methods and vehicles, an otherwise lethal dose of antiangiogenic chemotherapy can be used to treat tumors while minimizing systemic side effects. Current in-vitro and in-vivo animal studies have shown promising results that encourage the pursuit towards human clinical trials for localized antiangiogenic treatment in the near future.

Management of idiopathic spinal epidural lipomatosis: a case report and review of the literature.

BACKGROUND: Spinal epidural lipomatosis (SEL) is a rare pathologic growth of histologically normal unencapsulated adipose tissue in the epidural space. Although rare, SEL can compress the spinal cord or nerve roots causing myelopathy or radiculopathy. While SEL has been associated with long-term exposure to endogenous or exogenous steroids and obesity, idiopathic forms of SEL are much rarer. CASE REPORT: In this report, we present the first case of SEL isolated to the cervical region compressing the spinal cord in a healthy, non-obese, preadolescent patient. CONCLUSION: Idiopathic SEL in the pediatric population is a rare entity. This is the first case of epidural lipomatosis isolated to the cervical region in an adult or child patient. In refractory, symptomatic cases of idiopathic SEL, surgical decompression is often required.

Perioperative Retinal Artery Occlusion: Incidence and Risk Factors in Spinal Fusion Surgery From the US National Inpatient Sample 1998-2013.

BACKGROUND: Retinal artery occlusion (RAO) is a rare but devastating complication of spinal fusion surgery. We aimed to determine its incidence and associated risk factors. METHODS: Hospitalizations involving spinal fusion surgery were identified by searching the National Inpatient Sample, a database of hospital discharges, from 1998 to 2013. RAO cases were identified using ICD-9-CM codes. Using the STROBE guidelines, postulated risk factors were chosen based on literature review and identified using ICD-9-CM codes. Multivariate logistic models with RAO as outcome, and risk factors, race, age, admission, and surgery type evaluated associations. RESULTS: Of an estimated 4,784,275 spine fusions in the United States from 1998 to 2013, there were 363 (CI: 291-460) instances of RAO (0.76/10,000 spine fusions, CI: 0.61-0.96). Incidence ranged from 0.35/10,000 (CI: 0.11-1.73) in 2001-2002 to 1.29 (CI: 0.85-2.08) in 2012-2013, with no significant trend over time (P = 0.39). Most strongly associated with RAO were stroke, unidentified type (odds ratio, OR: 14.33, CI: 4.54-45.28, P < 0.001), diabetic retinopathy (DR) (OR: 7.00, CI: 1.18-41.66, P = 0.032), carotid stenosis (OR: 4.94, CI: 1.22-19.94, P = 0.025), aging (OR for age 71-80 years vs 41-50 years referent: 4.07, CI: 1.69-10.84, P = 0.002), and hyperlipidemia (OR: 2.96, CI: 1.85-4.73, P < 0.001). There was an association between RAO and transforaminal lumbar interbody fusion (OR: 2.95, CI: 1.29-6.75, P = 0.010). RAO was more likely to occur with spinal surgery performed urgently or emergently compared with being done electively (OR: 0.40, CI: 0.23-0.68, P < 0.001). CONCLUSIONS: Patient-specific associations with RAO in spinal fusion include aging, carotid stenosis, DR, hyperlipidemia, stroke, and specific types of surgery. DR may serve as an observable biomarker of heightened risk of RAO in patients undergoing spine fusion.

Introduction: the rise of the robots in spinal surgery.

In his 1920 science fiction play R.U.R., Czech writer Karel Capek introduced the word "robot" to the English language. The play tells the story of a factory that produces roboti, which are living creatures that resemble humans and have the capacity for individual thought. While at first the roboti seem content to work for their human masters, they later rebel, ultimately leading to the extinction of the human race. 1 This play and similar depictions of robots in literature and film are probably responsible for the slightly negative reputation of robots in general. Only recently has this perception changed, thanks to the advent of robots that can vacuum our houses and perform other mundane chores. Raymond Goertz, while working for the US Atomic Energy Commission, is credited with the development of the first robotic arm in 1951. 2 It was designed to handle hazardous radioactive material. Unimation Inc. developed the first industrial robot in 1961; that robot handled molten die-castings and removed the human element from these labor-intensive, often dangerous tasks. With the development of the Programmable Universal Manipulation Arm (PUMA) in 1978, the robot was sophisticated enough to be introduced to medicine. The first working definition of the word "robot" was published, fittingly, by the Robotics Institute of America in 1980: ". . . a reprogrammable, multifunctional manipulator designed to move materials, parts, tools, or specialized devices through various programmed motions for the performance of a variety of tasks." 6 In 1988, the six-degrees-of-freedom flexible arm PUMA 560 was used to guide a needle under CT guidance into the brain. 4 With the introduction of robotic arms came the ability to use them as surgical assistants. In 1998, Okada et al. described a voice-controlled robot used to hold a thoracoscope. 5 This type of robot was also used in thoracoscopic spinal surgery. The military, having a vested interest in telepresence surgery, helped fund the development of the da Vinci Surgical System that was approved for use by the FDA in 2000 and designed to facilitate complex, minimally invasive intracavitary surgeries. 7 In 2004, the FDA cleared the first commercially available positioning device for the placement of spinal instrumentation. At present, several systems are commercially available that utilize robotics for spinal operations. In a recent review, Joseph et al. evaluated the current landscape regarding safety, accuracy, and radiation exposure with the use of these technologies. These authors concluded that "… the placement of pedicle screws with robotics appears to be safe, and accuracy appears to be superior to freehand placement, although the data are not conclusive." 3 There seems to be a significant level of interest in this technology; however, only time will tell if it will become commonplace in our field. In this issue of Neurosurgical Focus, we visually explore the expanding role of robotics and image guidance in spinal surgery. New robots used for the first time and existing robots used for novel applications graphically demonstrate how our field is evolving. The days of fearing robots are behind us as members of our specialty begin to embrace the concept of automation. Thankfully, unlike Capek's rogue roboti, surgical robots rising up against us and causing world destruction is unlikely!

Image-guidance technology and the surgical resection of spinal column tumors.

Precision imaging is paramount to achieving success in surgical resection of many spinal tumors, whether the goal involves guiding a surgical cure for primary tumors or improving neurological decompression for metastatic lesions. Pre-operatively, image visualization is intimately involved with defining a clear target and surgical planning. Intra-operatively, image-guidance technology allows for surgeons to maximize the probability for gross total resection of spinal cord tumors and minimize damage to adjacent structures. Through this review, it is evident that spinal surgery has undergone significant advancements with the continued technological progression of different modalities of imaging guided technologies. Sophisticated imaging techniques compliment the surgeon's knowledge by providing an intraoperative reference to spinal column anatomy. This review discusses research efforts focusing on immersive imaging guided interactions with subject specific medical images that could enhance a surgeon's ability to plan and perform complex spinal oncology procedures with safety and efficiency.

Computational and In Vitro Experimental Investigation of Intrathecal Drug Distribution: Parametric Study of the Effect of Injection Volume, Cerebrospinal Fluid Pulsatility, and Drug Uptake.

BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters. The goal of this study is to demonstrate current computational capabilities to predict drug biodistribution while varying 3 parameters: (1) infusion settings, (2) drug chemistry, and (3) subject-specific anatomy and cerebrospinal fluid dynamics. We will discuss strategies to systematically optimize these 3 parameters to administer drug molecules to targeted tissue locations in the central nervous system. METHODS: We acquired anatomical data from magnetic resonance imaging (MRI) and velocity measurements in the spinal cerebrospinal fluid with CINE-MRI for 2 subjects. A bench-top surrogate of the subject-specific central nervous system was constructed to match measured anatomical dimensions and volumes. We generated a computational mesh for the bench-top model. Idealized simulations of tracer distribution were compared with bench-top measurements for validation. Using reconstructions from MRI data, we also introduced a subject-specific computer model for predicting drug spread for the human volunteer. RESULTS: MRI velocity measurements at 3 spinal regions of interest reasonably matched the simulated flow fields in a subject-specific computer mesh. Comparison between the idealized spine computations and bench-top tracer distribution experiments demonstrate agreement of our drug transport predictions to this physical model. Simulated multibolus drug infusion theoretically localizes drug to the cervical and thoracic region. Continuous drug pump and single bolus injection were successful to target the lumbar spine in the simulations. The parenchyma might be targeted suitably by multiple boluses followed by a flush infusion. We present potential guidelines that take into account drug specific kinetics for tissue uptake, which influence the speed of drug dispersion in the model and potentially influence tissue targeting. CONCLUSIONS: We present potential guidelines considering drug-specific kinetics of tissue uptake, which determine the speed of drug dispersion and influence tissue targeting. However, there are limitations to this analysis in that the parameters were obtained from an idealized healthy patient in a supine position. The proposed methodology could assist physicians to select clinical infusion parameters for their patients and provide guidance to optimize treatment algorithms. In silico optimization of intrathecal drug delivery therapies presents the first steps toward a possible care paradigm in the future that is specific to personalized patient anatomy and diseases.

Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid.

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.

Current status of intratumoral therapy for glioblastoma.

With emerging drug delivery technologies becoming accessible, more options are expected to become available to patients with glioblastoma (GBM) in the near future. It is important for clinicians to be familiar with the underlying mechanisms and limitations of intratumoral drug delivery, and direction of recent research efforts. Tumor-adjacent brain is an extremely complex living matrix that creates challenges with normal tissue intertwining with tumor cells. For convection-enhanced delivery (CED), the role of tissue anisotropy for better predicting the biodistribution of the infusate has recently been studied. Computational predictive methods are now available to better plan CED therapy. Catheter design and placement­in addition to the agent being used­are critical components of any protocol. This paper overviews intratumoral therapies for GBM, highlighting key anatomic and physiologic perspectives, selected agents (especially immunotoxins), and some new developments such as the description of the glymphatic system.

Intramedullary spinal cord tumors: a review of current and future treatment strategies.

Intramedullary spinal cord tumors have low incidence rates but are associated with difficult treatment options. The majority of patients with these tumors can be initially treated with an attempted resection. Unfortunately, those patients who cannot undergo gross-total resection or have subtotal resection are left with few treatment options, such as radiotherapy and chemotherapy. These adjuvant treatments, however, are associated with the potential for significant adverse side effects and still leave patients with a poor prognosis. To successfully manage these patients and improve both their quality of life and prognosis, novel treatment options must be developed to supplement subtotal resection. New research is underway investigating alternative therapeutic approaches for these patients, including directed, localized drug delivery and nanomedicine techniques. These and other future investigations will hopefully lead to promising new therapies for these devastating diseases.