A Survey Assessment of Neurosurgeons' Interest in Osteopathic Medicine and Its Integration Into Their Practice.

INTRODUCTION: Osteopathic manipulative medicine (OMM) encompasses techniques guided by the tenets of osteopathy aimed at facilitating the body's natural self-healing capabilities as a treatment option for injury or illness. This approach recognizes the interrelationship of structure and function in promoting overall health. The clinical applications of OMM have been highly researched throughout different subspecialties of medicine; however, there is a notable lack of osteopathic-based research targeted toward neurosurgical patient populations. METHODS: This cross-sectional descriptive study was conducted via a survey generated using SurveyMonkey (SurveyMonkey, San Mateo, CA, USA; accessed at www.surveymonkey.com). Subjects for this survey were gathered using a convenience sampling method in which emails of all neurosurgeons listed in the "Member Directory" on the American Association of Neurological Surgeons website were compiled into a mailing list. The survey was sent to all 6,503 emails collected, and the responses were recorded over the next month. The responses for each survey question were averaged and, when appropriate, compared using a two-tailed T-test, with statistical significance defined as a p<0.05. Where applicable, simple linear regression analysis was used to assess correlations between survey data. The measured outcomes included neurosurgeons' (1) knowledge of and (2) attitudes toward OMM. RESULTS: Both MD and DO neurosurgeons reported using OMM (or referring their patients for OMM) less than once per year. In comparison to their MD colleagues, neurosurgeons carrying a DO degree ranked their familiarity with the tenets of osteopathic medicine (p<0.0001) and their knowledge of the applications of OMM in their practice (p=0.0018) significantly higher. Greater reported familiarity with the tenets of osteopathic medicine and applications of OMM showed a positive correlation with neurosurgeons' comfort in recommending OMM as a nonsurgical, preoperative treatment option, as a post-surgical, rehabilitative treatment option, and as a pain management option (p<0.0001 for all). There was a clear interest in seeing further osteopathic-based neurosurgery research by both MD and DO neurosurgeons, as well as a trend of interest in incorporating OMM into their practice if shown to be clinically beneficial. CONCLUSIONS: Both MD and DO neurosurgeons are interested in seeing more research into the applications of OMM in their patient populations and, most importantly, are likely to integrate OMM into their practice if presented with research detailing clinical benefits to their patients. This study highlights the clinical interest of neurosurgeons in further research into the applications of OMM specific to the field of neurosurgery.

Length of Stay, Cost, and Outcomes related to Traumatic Subdural Hematoma in inpatient setting in the United States.

OBJECTIVE: In the US, the prevalence of traumatic subdural hematoma (TSDH) continues to increase. Using a nationally representative sample of discharge records of patients with TSDH, the study objectives were to estimate trend in number of TSDH cases, surgical management, inpatient cost, length of stay (LOS), mortality rate, and complication rate; and to identify the association of sociodemographic, clinical and hospital characteristics with complications and mortality. METHOD: We identified patients with a primary diagnosis of TSDH from the National Inpatient Sample (NIS) database from 2010 to 2017. Quarterly and monthly trends were estimated using interrupted time series design. Multivariate logistic regressions measured association between various factors and inpatient death and complications. RESULTS: Number of cases, mean LOS, rate of complication increased. Proportion of patients undergoing surgery, mean inpatient cost, inpatient mortality decreased. Mean inpatient cost was $23,182.40 and LOS was 6.41 days. Odds of inpatient death and complications increased with injury severity score and comorbid conditions requiring use of anticoagulants. Odds of inpatient death were highest among those ≥85 years old and in south and northeast region. CONCLUSION: Given the increase in prevalence of TSDH in USA, additional resources should be allocated toward improving patient outcomes and lowering healthcare costs.

Provision of rapid and specific ex vivo diagnosis of central nervous system lymphoma from rodent xenograft biopsies by a fluorescent aptamer.

OBJECTIVE: Differentiating central nervous system (CNS) lymphoma from other intracranial malignancies remains a clinical challenge in surgical neuro-oncology. Advances in clinical fluorescence imaging contrast agents and devices may mitigate this challenge. Aptamers are a class of nanomolecules engineered to bind cellular targets with antibody-like specificity in a fraction of the staining time. Here, the authors determine if immediate ex vivo fluorescence imaging with a lymphoma-specific aptamer can rapidly and specifically diagnose xenografted orthotopic human CNS lymphoma at the time of biopsy. METHODS: The authors synthesized a fluorescent CNS lymphoma-specific aptamer by conjugating a lymphoma-specific aptamer with Alexa Fluor 488 (TD05-488). They modified human U251 glioma cells and Ramos lymphoma cells with a lentivirus for constitutive expression of red fluorescent protein and implanted them intracranially into athymic nude mice. Three to 4 weeks postimplantation, acute slices (biopsies, n = 28) from the xenografts were collected, placed in aptamer solution, and imaged with a Zeiss fluorescence microscope. Three aptamer staining concentrations (0.3, 1.0, and 3.0 µM) and three staining times (5, 10, and 20 minutes) followed by a 1-minute wash were tested. A file of randomly selected images was distributed to neurosurgeons and neuropathologists, and their ability to distinguish CNS lymphoma from negative controls was assessed. RESULTS: The three staining times and concentrations of TD05-488 were tested to determine the diagnostic accuracy of CNS lymphoma within a frozen section time frame. An 11-minute staining protocol with 1.0-µM TD05-488 was most efficient, labeling 77% of positive control lymphoma cells and less than 1% of negative control glioma cells (p < 0.001). This protocol permitted clinicians to positively identify all positive control lymphoma images without misdiagnosing negative control images from astrocytoma and normal brain. CONCLUSIONS: Ex vivo fluorescence imaging is an emerging technique for generating rapid histopathological diagnoses. Ex vivo imaging with a novel aptamer-based fluorescent nanomolecule could provide an intraoperative tumor-specific diagnosis of CNS lymphoma within 11 minutes of biopsy. Neurosurgeons and neuropathologists interpreted images generated with this molecular probe with high sensitivity and specificity. Clinical application of TD05-488 may permit specific intraoperative diagnosis of CNS lymphoma in a fraction of the time required for antibody staining.

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials.

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources.

Pediatric spinal cord biopsy: A case series from a high-volume referral center.

Pediatric patients presenting with intramedullary spinal cord lesions often require specific diagnoses to guide their treatment plans. Though results from magnetic resonance imaging and lumbar puncture may narrow the differential diagnosis, these tests cannot always provide a definitive diagnosis. In such cases, spinal cord biopsy may be undertaken to provide a specific histopathologic diagnosis for guiding treatment. Data from the adult population show 24% of spinal cord biopsies can be nondiagnostic and the procedure may carry a 21% complication rate. Therefore, spinal cord biopsy may portend a similar high risk-to-benefit ratio in the pediatric population. Here, we review spinal cord biopsy cases scheduled for diagnosis, and not debulking, at a high volume pediatric referral center during a seventeen-year period. We report our experience with five patients who met our inclusion criteria. Due to the rarity of the procedure, statistically significant factors associated with improved diagnostic yield or peri-operative complication could not be identified. A definitive diagnosis which guided the post-operative treatment plan was obtained in four of our five patients. None of our patients developed post-operative motor deficits. However, these patients were susceptible to the same risks of open spine surgery, such as wound infections and spinal deformities. Our case series shows that intramedullary spinal cord biopsies may provide tissue for obtaining histopatholgic diagnoses. However, the potential risks of complication, and the possibility of obtaining nondiagnostic tissue, should be discussed with patients, families and their medical treatment teams.

Neurosurgical Flexible Probe Microscopy with Enhanced Architectural and Cytological Detail.

BACKGROUND: Microscopic delineation and clearance of tumor cells at neurosurgical excision margins potentially reduce tumor recurrence and increase patient survival. Probe-based in vivo fluorescence microscopy technologies are promising for neurosurgical in vivo microscopy. OBJECTIVE: We sought to demonstrate a flexible fiberoptic epifluorescence microscope capable of enhanced architectural and cytological imaging for in vivo microscopy during neurosurgical procedures. METHODS: Eighteen specimens were procured from neurosurgical procedures. These specimens were stained with acridine orange and imaged with a 3-dimensional (3D)-printed epifluorescent microscope that incorporates a flexible fiberoptic probe. Still images and video sequence frames were processed using frame alignment, signal projection, and pseudo-coloring, resulting in resolution enhancement and an increased field of view. RESULTS: Images produced displayed good nuclear contrast and architectural detail. Grade 1 meningiomas demonstrated 3D chords and whorls. Low-grade meningothelial nuclei showed streaming and displayed regularity in size, shape, and distribution. Oligodendrogliomas showed regular round nuclei and a variably staining background. Glioblastomas showed high degrees of nuclear pleomorphism and disarray. Mitoses, vascular proliferation, and necrosis were evident. CONCLUSIONS: We demonstrate the utility of a 3D-printed, flexible probe microscope for high-resolution microscopic imaging with increased architectural detail. Enhanced in vivo imaging using this device may improve our ability to detect and decrease microscopic tumor burden at excision margins during neurosurgical procedures.

Epithelioid glioblastoma presenting as aphasia in a young adult with ovarian cancer: A case report.

Our patient's clinical history and preoperative radiographic evaluation suggested central nervous system (CNS) metastatic disease. Ultimately, final pathology revealed epithelioid glioblastoma (eGBM), a newly classified CNS primary tumor. This reinforces the importance of direct tissue sampling and including eGBM on the differential for young patients with histories of systemic cancer presenting with new CNS lesions.

Fluorescence-guided stereotactic biopsy: a proof-of-concept study.

OBJECTIVEAccurate histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining suspicious tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in some cases. Failure to obtain diagnostic tissue can delay initiation of treatment and may result in further invasive procedures for patients. In this study, the authors sought to determine if the coupling of in vivo optical imaging with an STB system is an effective method for identification of diagnostic tissue at the time of biopsy.METHODSA minimally invasive fiber optic imaging system was developed by coupling a 0.65-mm-diameter coherent fiber optic fluorescence microendoscope to an STB system. Human U251 glioma cells were transduced for stable expression of blue fluorescent protein (BFP) to produce U251-BFP cells that were utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by fluorescein sodium (FNa) was quantified with fluorescence microscopy. In vivo, transgenic athymic rats implanted with U251-BFP cells (n = 4) were utilized for experiments. Five weeks postimplantation, the rats received 5-10 mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65-mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest ipsilateral and contralateral to tumor implantation were obtained and quantified.RESULTSLive-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2 = 0.91, p < 0.001). Normalized to background, in vivo FNa-mediated fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (301.7 ± 34.18 relative fluorescence units, p < 0.001). Fluorescence intensity measured from the tumor margin was not significantly greater than that from normal brain (p = 0.89). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor.CONCLUSIONSThe authors found that in vivo fluorescence imaging with an STB needle containing a submillimeter-diameter fiber optic fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. These results were confirmed in vivo with positive control cells and by post hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies.

Acridine Orange as a Novel Photosensitizer for Photodynamic Therapy in Glioblastoma.

BACKGROUND: Photodynamic therapy combines the effects of a chemical agent with the physical energy from light or radiation to result in lysis of cells. Acridine orange (AO) is a molecule with fluorescence properties that has been demonstrated to possess photosensitizing properties. The objective of this study was to investigate the photodynamic effect of AO on glioblastoma cell viability and growth. METHODS: Glioblastoma cells (N = 8000 cells/well at 0 hours) were exposed to AO followed by white unfiltered light-emitting diode light. Cultures were exposed to either 10 or 30 minutes of light. The cell number per well was determined at 0, 24, 48, and 72 hours after exposure. RESULTS: A dramatic cytocidal effect of AO after exposure to 10 minutes of white light was observed. There was almost complete eradication of glioblastoma cells over a 72-hour period. Although AO or light alone exhibited some effect on cell growth, it was not as pronounced as the combination of AO and light. CONCLUSIONS: This is the first study to our knowledge to demonstrate the photodynamic effect of AO in glioblastoma cells. These data support the need for further studies to characterize and evaluate whether this striking cytotoxic effect can be achieved in vivo. The combination of AO and exposure to white unfiltered light-emitting diode light may have potential future applications in management of glioblastoma.

In Vivo Microscopy in Neurosurgical Oncology.

Intraoperative neurosurgical histopathologic diagnoses rely on evaluation of rapid tissue preparations such as frozen sections and smears with conventional light microscopy. Although useful, these techniques are time consuming and therefore cannot provide real-time intraoperative feedback. In vivo molecular imaging techniques are emerging as novel methods for generating real-time diagnostic histopathologic images of tumors and their surrounding tissues. These imaging techniques rely on contrast generated by exogenous fluorescent dyes, autofluorescence of endogenous molecules, fluorescence decay of excited molecules, or light scattering. Large molecular imaging instruments are being miniaturized for clinical in vivo use. This review discusses pertinent imaging systems that have been developed for neurosurgical use and imaging techniques currently under development for neurosurgical molecular imaging.

Novel free-hand T1 pedicle screw method: Review of 44 consecutive cases.

SUMMARY OF BACKGROUND DATA: Multilevel posterior cervical instrumented fusions are becoming more prevalent in current practice. Biomechanical characteristics of the cervicothoracic junction may necessitate extending the construct to upper thoracic segments. However, fixation in upper thoracic spine can be technically demanding owing to transitional anatomy while suboptimal placement facilitates vascular and neurologic complications. Thoracic instrumentation methods include free-hand, fluoroscopic guidance, and CT-based image guidance. However, fluoroscopy of upper thoracic spine is challenging secondary to vertebral geometry and patient positioning, while image-guided systems present substantial financial commitment and are not readily available at most centers. Additionally, imaging modalities increase radiation exposure to the patient and surgeon while potentially lengthening surgical time. MATERIALS AND METHODS: Retrospective review of 44 consecutive patients undergoing a cervicothoracic fusion by a single surgeon using the novel free-hand T1 pedicle screw technique between June 2009 and November 2012. A starting point medial and cephalad to classic entry as well as new trajectory were utilized. No imaging modalities were employed during screw insertion. Postoperative CT scans were obtained on day 1. Screw accuracy was independently evaluated according to the Heary classification. RESULTS: In total, 87 pedicle screws placed were at T1. Grade 1 placement occurred in 72 (82.8%) screws, Grade 2 in 4 (4.6%) screws and Grade 3 in 9 (10.3%) screws. All Grade 2 and 3 breaches were <2 mm except one Grade 3 screw breaching 2-4 mm laterally. Only two screws (2.3%) were noted to be Grade 4, both breaching medially by less than 2 mm. No new neurological deficits or returns to operating room took place postoperatively. CONCLUSIONS: This modification of the traditional starting point and trajectory at T1 is safe and effective. It attenuates additional bone removal or imaging modalities while maintaining a high rate of successful screw placement compared to historical controls.

Thoracolumbar instrumentation with CT-guided navigation (O-arm) in 270 consecutive patients: accuracy rates and lessons learned.

OBJECT: Thoracolumbar instrumentation has experienced a dramatic increase in utilization over the last 2 decades. However, pedicle screw fixation remains a challenging undertaking, with suboptimal placement contributing to postoperative pain, neurological deficit, vascular complications, and return to the operating suite. Image-guided spinal surgery has substantially improved the accuracy rates for these procedures. However, it is not without technical challenges and a learning curve for novice operators. The authors present their experience with the O-arm intraoperative imaging system and share the lessons they learned over nearly 5 years. METHODS: The authors performed a retrospective chart review of 270 consecutive patients who underwent thoracolumbar pedicle screw fixation utilizing the O-arm imaging system in conjunction with StealthStation navigation between April 2009 and September 2013 at a single tertiary care center; 266 of the patients underwent CT scanning on postoperative Day 1 to evaluate hardware placement. The CT scans were interpreted prospectively by 3 neuroradiologists as part of standard work flow and retrospectively by 2 neurosurgeons and a senior resident. Pedicle screws were evaluated for breaches according to the 3-tier classification proposed by Mirza et al. RESULTS: Of 270 patients, 266 (98.5%) were included in the final analysis based on the presence of a postoperative CT scan. Overall, 1651 pedicle screws were placed in 266 patients and yielded a 5.3% breach rate; 213 thoracic and 1438 lumbosacral pedicle screws were inserted with 6.6% and 5.1% breach rates, respectively. Of the 87 suboptimally placed screws, there were 13 Grade 1, 16 Grade 2, and 12 Grade 3 misses as well as 46 anterolateral or "tip-out" perforations at L-5. Four patients (1.5%) required a return to the operating room for pedicle screw revision, 2 of whom experienced transient radicular symptoms and 2 remained asymptomatic. Interestingly, the pedicle breach rate was higher than anticipated at 13.21% for the 30 patients over the initial 6-month period with the O-arm. After certain modifications to the authors' technique, the subsequent 30 patients experienced a statistically significant decrease in breach rate at 5.6% (p = 0.014). CONCLUSIONS: Image-guided spinal surgery can be a great option in the operating room and provides high pedicle screw accuracy rates. With numerous systems commercially available, it is important to develop a systematic approach regardless of the technology in question. There is a learning curve for surgeons unfamiliar with image guidance that should be recognized and appreciated when transitioning to navigation-assisted spinal surgery. In fact, the authors' experience with a large patient cohort suggests that this learning curve may be more significant than previously reported.

Contemporary Approaches to the Management of Neurosurgical Complications of Infective Endocarditis.

Infective endocarditis can often involve the nervous system, resulting in stroke, intracerebral hemorrhage, infectious aneurysm formation, cerebral abscess, and spinal epidural infection. Many of these problems require neurosurgical attention. Modern advances in neuro- surgical critical care, computerization, instrumentation, and radiologic imaging have affected the treatments available to patients with neurosurgical manifestations of infective endocarditis. This paper is a brief overview of the contemporary management of neurosurgical complications of infective endocarditis.