Intraoperative confocal laser endomicroscopy: prospective in vivo feasibility study of a clinical-grade system for brain tumors.

OBJECTIVE: The authors evaluated the feasibility of using the first clinical-grade confocal laser endomicroscopy (CLE) system using fluorescein sodium for intraoperative in vivo imaging of brain tumors. METHODS: A CLE system cleared by the FDA was used in 30 prospectively enrolled patients with 31 brain tumors (13 gliomas, 5 meningiomas, 6 other primary tumors, 3 metastases, and 4 reactive brain tissue). A neuropathologist classified CLE images as interpretable or noninterpretable. Images were compared with corresponding frozen and permanent histology sections, with image correlation to biopsy location using neuronavigation. The specificities and sensitivities of CLE images and frozen sections were calculated using permanent histological sections as the standard for comparison. A recently developed surgical telepathology software platform was used in 11 cases to provide real-time intraoperative consultation with a neuropathologist. RESULTS: Overall, 10,713 CLE images from 335 regions of interest were acquired. The mean duration of the use of the CLE system was 7 minutes (range 3-18 minutes). Interpretable CLE images were obtained in all cases. The first interpretable image was acquired within a mean of 6 (SD 10) images and within the first 5 (SD 13) seconds of imaging; 4896 images (46%) were interpretable. Interpretable image acquisition was positively correlated with study progression, number of cases per surgeon, cumulative length of CLE time, and CLE time per case (p ≤ 0.01). The diagnostic accuracy, sensitivity, and specificity of CLE compared with frozen sections were 94%, 94%, and 100%, respectively, and the diagnostic accuracy, sensitivity, and specificity of CLE compared with permanent histological sections were 92%, 90%, and 94%, respectively. No difference was observed between lesion types for the time to first interpretable image (p = 0.35). Deeply located lesions were associated with a higher percentage of interpretable images than superficial lesions (p = 0.02). The study met the primary end points, confirming the safety and feasibility and acquisition of noninvasive digital biopsies in all cases. The study met the secondary end points for the duration of CLE use necessary to obtain interpretable images. A neuropathologist could interpret the CLE images in 29 (97%) of 30 cases. CONCLUSIONS: The clinical-grade CLE system allows in vivo, intraoperative, high-resolution cellular visualization of tissue microstructure and identification of lesional tissue patterns in real time, without the need for tissue preparation.

Redosing of Fluorescein Sodium Improves Image Interpretation During Intraoperative Ex Vivo Confocal Laser Endomicroscopy of Brain Tumors.

BACKGROUND: Fluorescein sodium (FNa) is a fluorescence agent used with a wide-field operating microscope for intraoperative guidance and with confocal laser endomicroscopy (CLE) to evaluate brain tissue. Susceptibility of FNa to degradation over time may affect CLE image quality during prolonged surgeries. This study describes improved characteristics of CLE images after intraoperative redosing with FNa. METHODS: A retrospective analysis was performed using CLE images obtained ex vivo from samples obtained during tumor resections with FNa-based fluorescence guidance with a wide-field operating microscope. The comparison groups included CLE images acquired after FNa redosing (redose imaging group), images from the same patients acquired after the initial FNa dose (initial-dose imaging group), and images from patients in whom redosing was not used (single-dose imaging group). A detailed assessment of image quality and interpretation regarding different FNa dosage and timing of imaging after FNa administration was conducted for all comparison groups. RESULTS: The brightest and most contrasting images were observed in the redose group compared to the initial-dose and single-dose groups (P<0.001). The decay of FNa signal negatively correlated with brightness (rho = -0.52, P<0.001) and contrast (rho = -0.57, P<0.001). Different doses of FNa did not significantly affect the brightness (P=0.15) or contrast (P=0.09) in CLE images. As the mean timing of imaging increased, the percentage of accurately diagnosed images decreased (P=0.03). CONCLUSIONS: The decay of the FNa signal is directly associated with image brightness and contrast. The qualitative interpretation scores of images were highest for the FNa redose imaging group. Redosing with FNa to improve the utility of CLE imaging should be considered a safe and beneficial strategy during prolonged surgeries.

Partial high frequency nerve block decreases neuropathic signaling following chronic sciatic nerve constriction injury.

Objective.High frequency (HF) block can quickly and reversibly stop nerve conduction. We hypothesized HF block at the sciatic nerve would minimize nociception by preventing neuropathic signals from reaching the central nervous system.Approach.Lewis rats were implanted with a constriction cuff and a distal cuff electrode around their right sciatic nerve. Tactile sensitivity was evaluated using the 50% paw withdrawal threshold (PWT) determined using Chaplan's method for von Frey monofilaments. Over the course of 49 d, the 50% PWT was measured (1) before HF block, (2) during HF block (50 kHz, 3Vpp), and (3) after HF block. Gait was observed and scored before and during block. At end point, HF block efficacy was directly evaluated using additional cuff electrodes to elicit and record compound neural action potentials across the HF blocking cuff.Main results.At days 7 and 14 d post-operation, tactile sensitivity was significantly lower during HF block compared to before and after block (p< 0.005). Additionally, an increase in gait disability was not visually observed during HF block.Significance.HF block can reduce tactile sensitivity in a limb with a neuropthic injury in a rapidly reversible fashion.

Cervical Spine Deformity Correction Techniques.

Cervical kyphotic deformity can be a debilitating condition with symptoms ranging from mechanical neck pain, radiculopathy, and myelopathy to impaired swallowing and horizontal gaze. Surgical correction of cervical kyphosis has the potential to halt progression of neurological and clinical deterioration and even restore function. There are various operative approaches and deformity correction techniques. Choosing the optimal strategy is predicated on a fundamental understanding of spine biomechanics. Preoperative characterization of cervical malalignment, assessment of deformity rigidity, and defining postoperative clinical and radiographic objectives are paramount to formulating a surgical plan that balances clinical benefit with morbidity. This review of cervical deformity treatment provides an overview of the biomechanics of cervical kyphosis, radiographic classification, algorithm-based management, surgical techniques, and current surgical outcome studies.

Does Ossification of the Posterior Longitudinal Ligament Progress After Fusion?

Starting in the 1960s, ossification of the posterior longitudinal ligament (OPLL) became more commonly diagnosed in Japan. The disease is characterized by a gradual increase in calcification of the posterior longitudinal ligament with the eventual sequelae of cervical canal stenosis and myelopathy. Surgical interventions to relieve stenosis and neurologic symptoms are performed to decompress the cervical canal. Studies demonstrate continued ossification of the OPLL in both nonsurgical and surgically treated patients. In this review, the authors evaluate the epidemiology, pathophysiology, and literature regarding disease progression in OPLL after cervical fusion.

Reimbursement patterns for neurosurgery: Analysis of the NERVES survey results from 2011-2016.

OBJECTIVE: In response to rising national health expenditures, the Patient Protection and Affordable Care Act (ACA) was passed in 2010, with major provisions implemented in 2014. Due to increasing concerns about workload and compensation among neurosurgeons, we evaluated trends in neurosurgical reimbursement, productivity and compensation before and after the implementation of the major provisions of the ACA. PATIENTS AND METHODS: Results from Neurosurgery Executives' Resource Value and Education Society (NERVES) annual surveys were collected, representing data from 2011 to 2016. Responses from different practice settings across the six years were categorized into groups, and inverse variance-weighted averaging was performed within the frameworks of a one-way ANOVA model with year. Data from 2011 to 2013 and 2014-2016 were analyzed similarly for differences among practice setting and region. RESULTS: The NERVES survey response rates ranged from 20% to 36%. Median values for compensation decreased by 3.66%, 6.42%, and 10.34% within private, hospital, and academic practices respectively after 2014 although these trends did not reach statistical significance. Median work RVUs had a trend to decrease by 5.67%, 13.08%, and 19.44% within private, hospital, and academic practices respectively after 2014. Academic practices showed statistically significant decreases in annual total RVUs, total gross charges and collections. CONCLUSION: These data demonstrate neurosurgical reimbursement and productivity have trended down during a time that increases in productivity and reimbursement were predicted. This phenomenon is most notable in academic practices compared to private or hospital based practices. Prospective analyses of the impact of healthcare policy reform on neurosurgical productivity are urgently needed.

Race and socioeconomic disparity in treatment and outcome of traumatic cervical spinal cord injury with fracture: Nationwide Inpatient Sample database, 1998-2009.

STUDY DESIGN: A retrospective national administrative database study. OBJECTIVE: Advances in treatment of traumatic cervical spinal cord injury with fracture (TCSCIF) have led to significant improvements in clinical outcomes; however, progress in healthcare is seldom ubiquitous across demographic groups. Therefore, we explored if disparities in treatment and outcome after TCSCIF exist across race and socioeconomic status. SETTING: USA. METHODS: We queried the Nationwide Inpatient Sample database from 1998 to 2009 for TCSCIF hospitalizations. Multivariate analysis was used to identify the correlation between socioeconomic status and race to injury, treatment type, and outcome. RESULTS: There were 21,985 admissions for TCSCIF, 66.9% of whom had a favorable discharge disposition. In-hospital mortality rate was 12.5%. A total of 43.7% underwent surgery. Overall, surgery was associated with lower in-hospital mortality (OR 0.30, 95% CI 0.27-0.34, p < 0.01) and better discharge disposition (OR 0.68, 95% CI 0.62-0.74, p < 0.01) versus nonsurgical or no intervention. African-American (AA) race and low socioeconomic status (LSES) were significant predictors of lower odds to undergo surgery and unfavorable discharge disposition, respectively; potentially explained by a higher odds of increased New Injury Severity Score classification at presentation. Surgical and favorable discharge rates for LSES and non-Caucasian races, however, have been steadily improving over the study period. CONCLUSIONS: Despite trending improved outcomes after TCSCIF, LSES, or AA race were more likely to have worse outcomes compared to their counterparts. In addition, LSES, AA, and Hispanic groups were less likely to undergo surgical treatment, suggesting disparities in management and outcome effect.

Correlation of perioperative risk scores with hospital costs in neurosurgical patients.

OBJECTIVE: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online surgical risk calculator uses inherent patient characteristics to provide predictive risk scores for adverse postoperative events. The purpose of this study was to determine if predicted perioperative risk scores correlate with actual hospital costs. METHODS: A single-center retrospective review of 1005 neurosurgical patients treated between September 1, 2011, and December 31, 2014, was performed. Individual patient characteristics were entered into the NSQIP calculator. Predicted risk scores were compared with actual in-hospital costs obtained from a billing database. Correlational statistics were used to determine if patients with higher risk scores were associated with increased in-hospital costs. RESULTS: The Pearson correlation coefficient (R) was used to assess the correlation between 11 types of predicted complication risk scores and 5 types of encounter costs from 1005 health encounters involving neurosurgical procedures. Risk scores in categories such as any complication, serious complication, pneumonia, cardiac complication, surgical site infection, urinary tract infection, venous thromboembolism, renal failure, return to operating room, death, and discharge to nursing home or rehabilitation facility were obtained. Patients with higher predicted risk scores in all measures except surgical site infection were found to have a statistically significant association with increased actual in-hospital costs (p < 0.0005). CONCLUSIONS: Previous work has demonstrated that the ACS NSQIP surgical risk calculator can accurately predict mortality after neurosurgery but is poorly predictive of other potential adverse events and clinical outcomes. However, this study demonstrates that predicted high-risk patients identified by the ACS NSQIP surgical risk calculator have a statistically significant moderate correlation to increased actual in-hospital costs. The NSQIP calculator may not accurately predict the occurrence of surgical complications (as demonstrated previously), but future iterations of the ACS universal risk calculator may be effective in predicting actual in-hospital costs, which could be advantageous in the current value-based healthcare environment.

Radiographic and Neurological Outcome After Surgical Treatment of Traumatic Fractures of the Ankylotic Thoracic Spine: A Retrospective Case Series.

BACKGROUND: Spontaneous thoracic ankylosis is a progressive degenerative process that predisposes patients to potentially highly unstable traumatic injuries. Acute hyperextension fractures result in dynamic instability putting the spinal cord at risk. OBJECTIVE: To describe preoperative radiographic characteristics of fractures of the ankylotic thoracic spine and relate findings to early postoperative radiographic and clinical outcomes. METHODS: A single center, retrospective review was performed of 28 surgically treated patients with fractures of the ankylotic thoracic spine. Radiographic assessment included preoperative fracture angulation (FA) and fracture displacement (FD), and postoperative change in sagittal alignment. Early clinical outcomes included preoperative and postoperative American Spinal Injury Association (ASIA) grade and perioperative complications. RESULTS: Seven patients (25%) presented with poor neurological grade (ASIA A-C) compared to 21 (75%) with good grade (ASIA D, E). At presentation, poor grade patients had a mean FA of 16.4° (range 0°-34.5°), and FD of 7.76 mm (range 0.8-9.2). Good grade patients had a mean FA of 18.2° (range 0°-43.3°), and FD of 4.77 mm (range 0-25.1). There was no statistically significant difference in FA or FD between groups (P = .70 and .20 respectively). All underwent posterior pedicle screw fixation for stabilization. Fifty per cent of patients presenting with ASIA C or D spinal cord injury improved 1 or more ASIA grades. There were no perioperative complications. Early postoperative sagittal alignment was maintained with a mean change of -2.6°. CONCLUSION: Presenting fracture alignment does not significantly correlate with pre- or postoperative neurological status. Early posterior stabilization preserved neurological function, with neurological recovery occurring in a portion of individuals.

Impact of Timing of Intervention Among 397 Consecutively Treated Brainstem Cavernous Malformations.

BACKGROUND: Surgical resection of brainstem cavernous malformations (BSCMs) is challenging, and patient selection and timing of intervention remain controversial. OBJECTIVE: To evaluate the impact of surgical timing and predictors of neurological outcome after surgical resection of BSCMs. METHODS: Consecutive adult patients (≥18 years) with BSCMs undergoing surgical resection between 1985 and 2014 by the senior author (RFS) were retrospectively reviewed. Patient demographics, lesion characteristics, imaging results, surgical approach, and perioperative and long-term neurological morbidity were analyzed. RESULTS: Data were analyzed for a total of 397 adult patients (160, 40% male). On univariate analysis, a greater proportion of patients treated within 6 weeks of hemorrhage had an improved Glasgow Outcome Scale score (P = .06). On logistic regression analysis, patients treated within 6 weeks of hemorrhage experienced improved clinical outcomes (odds ratio = 1.73; 95% confidence interval = 1.06-2.83; P = .03). CONCLUSIONS: Although BSCM surgery is associated with significant perioperative morbidity and mortality, favorable long-term hemorrhage rates and symptom resolution can be achieved in a carefully selected group of patients. Overall, patients treated acutely, within 6 weeks, benefited the most from surgical intervention.

Chen Jingrun, China's famous mathematician: devastated by brain injuries on the doorstep to solving a fundamental mathematical puzzle.

Chen Jingrun (1933-1996), perhaps the most prodigious mathematician of his time, focused on the field of analytical number theory. His work on Waring's problem, Legendre's conjecture, and Goldbach's conjecture led to progress in analytical number theory in the form of "Chen's Theorem," which he published in 1966 and 1973. His early life was ravaged by the Second Sino-Japanese War and the Chinese Cultural Revolution. On the verge of solving Goldbach's conjecture in 1984, Chen was struck by a bicyclist while also bicycling and suffered severe brain trauma. During his hospitalization, he was also found to have Parkinson's disease. Chen suffered another serious brain concussion after a fall only a few months after recovering from the bicycle crash. With significant deficits, he remained hospitalized for several years without making progress while receiving modern Western medical therapies. In 1988 traditional Chinese medicine experts were called in to assist with his treatment. After a year of acupuncture and oxygen therapy, Chen could control his basic bowel and bladder functions, he could walk slowly, and his swallowing and speech improved. When Chen was unable to produce complex work or finish his final work on Goldbach's conjecture, his mathematical pursuits were taken up vigorously by his dedicated students. He was able to publish Youth Math, a mathematics book that became an inspiration in Chinese education. Although he died in 1996 at the age of 63 after surviving brutal political repression, being deprived of neurological function at the very peak of his genius, and having to be supported by his wife, Chen ironically became a symbol of dedication, perseverance, and motivation to his students and associates, to Chinese youth, to a nation, and to mathematicians and scientists worldwide.