Image-Guided Navigation in Spine Surgery: From Historical Developments to Future Perspectives.

Intraoperative navigation is critical during spine surgery to ensure accurate instrumentation placement. From the early era of fluoroscopy to the current advancement in robotics, spinal navigation has continued to evolve. By understanding the variations in system protocols and their respective usage in the operating room, the surgeon can use and maximize the potential of various image guidance options more effectively. At the same time, maintaining navigation accuracy throughout the procedure is of the utmost importance, which can be confirmed intraoperatively by using an internal fiducial marker, as demonstrated herein. This technology can reduce the need for revision surgeries, minimize postoperative complications, and enhance the overall efficiency of operating rooms.

Application of Machine Learning Strategies to Model the Effects of Sevoflurane on Somatosensory-Evoked Potentials during Spine Surgery.

In this study, a small sample of patients' neuromonitoring data was analyzed using machine learning (ML) tools to provide proof of concept for quantifying complex signals. Intraoperative neurophysiological monitoring (IONM) is a valuable asset for monitoring the neurological status of a patient during spine surgery. Notably, this technology, when operated by neurophysiologists and surgeons familiar with proper alarm criteria, is capable of detecting neurological deficits. However, non-surgical factors, such as volatile anesthetics like sevoflurane, can negatively influence robust IONM signal generation. While sevoflurane has been shown to affect the latency and amplitude of somatosensory evoked potential (SSEP), a more complex and nuanced analysis of the SSEP waveform has not been performed. In this study, signal processing and machine learning techniques were used to more intricately characterize and predict SSEP waveform changes as a function of varying end-tidal sevoflurane concentration. With data from ten patients who underwent spinal procedures, features describing the SSEP waveforms were generated using principal component analysis (PCA), phase space curves (PSC), and time-frequency analysis (TFA). A minimum redundancy maximum relevance (MRMR) feature selection technique was then used to identify the most important SSEP features associated with changing sevoflurane concentrations. Once the features carrying the maximum amount of information about the majority of signal waveform variability were identified, ML models were used to predict future changes in SSEP waveforms. Linear regression, regression trees, support vector machines, and neural network ML models were then selected for testing. Using SSEP data from eight patients, the models were trained using a range of features selected during MRMR calculations. During the training phase of model development, the highest performing models were identified as support vector machines and regression trees. After identifying the highest performing models for each nerve group, we tested these models using the remaining two patients' data. We compared the models' performance metrics using the root mean square error values (RMSEs). The feasibility of the methodology described provides a general framework for the applications of machine learning strategies to further delineate the effects of surgical and non-surgical factors affecting IONM signals.

The Use of Intraoperative Neuromonitoring for Cervical Spine Surgery: Indications, Challenges, and Advances.

Intraoperative neuromonitoring (IONM) has become an indispensable surgical adjunct in cervical spine procedures to minimize surgical complications. Understanding the historical development of IONM, indications for use, associated pitfalls, and recent developments will allow the surgeon to better utilize this important technology. While IONM has shown great promise in procedures for cervical deformity, intradural tumors, or myelopathy, routine use in all cervical spine cases with moderate pathology remains controversial. Pitfalls that need to be addressed include human error, a lack of efficient communication, variable alarm warning criteria, and a non-standardized checklist protocol. As the techniques associated with IONM technology become more robust moving forward, IONM emerges as a crucial solution to updating patient safety protocols.

The Impact of C1 Anterior Arch Preservation on Spine Stability After Odontoidectomy: Systematic Review and Meta-Analysis.

BACKGROUND: Odontoidectomy for symptomatic irreducible ventral brainstem compression at the craniovertebral junction may result in spine instability requiring subsequent instrumentation. There is no consensus on the importance of C1 anterior arch preservation in prevention of iatrogenic instability. We conducted a systematic review of the impact of C1 anterior arch preservation on postodontoidectomy spine stability. METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients undergoing odontoidectomy. Random-effect model meta-analyses were performed to compare spine stability between C1 anterior arch preservation versus removal and posttreatment outcomes between transoral approaches (TOAs) versus endoscopic endonasal approaches (EEAs). RESULTS: We included 27 studies comprising 462 patients. The most common lesions were basilar invagination (73.3%) and degenerative arthritis (12.6%). Symptoms included myelopathy (72%) and neck pain (43.9%). Odontoidectomy was performed through TOA (56.1%) and EEA corridors (34.4%). The C1 anterior arch was preserved in 16.7% of cases. Postodontoidectomy stabilization was performed in 83.3% patients. Median follow-up was 27 months (range, 0.1-145). Rates of spine instability were significantly lower (P = 0.004) when the C1 anterior arch was preserved. Postoperative clinical improvement and pooled complications were reported in 78.8% and 12.6% of patients, respectively, with no significant differences between TOA and EEA (P = 0.892; P = 0.346). Patients undergoing EEA had significantly higher rates of intraoperative cerebrospinal fluid leaks (P = 0.002). CONCLUSIONS: Odontoidectomy is safe and effective for treating craniovertebral junction lesions. Preservation of the C1 anterior arch seems to improve maintenance of spine stability. TOA and EEA show comparable outcomes and complication rates.

Retrospective Data Analysis and Literature Review for a Development of Enhanced Recovery after Surgery Pathway for Anterior Cervical Discectomy and Fusion.

Objective While enhanced recovery after surgery (ERAS) protocols are associated with shorter length of stay and improved outcomes in multiple surgical specialties, its application to spine surgery has been limited. Anterior cervical discectomy and fusion (ACDF) is a common spinal procedure with a relative efficacy and safety profile that makes it suitable for the application of ERAS principles. Reviewing our outcomes and practice and incorporating evidence-based clinical studies, we propose the development of an ERAS pathway for ACDF. Methods This is a retrospective review of ACDF cases performed at a single institution by a single surgeon from 2014 to 2017. Primary outcome measures included length of stay, complications, and 30-day readmission rates. The 1- and 2-level and the 3- and 4-level groups were also each consolidated into a single cohort for comparison. A comprehensive review of evidence-based literature pertaining to ACDF was then performed. Best-practice recommendations derived from the literature were incorporated into the proposed ERAS protocol. Results In this series of 75 1-level, 77 2-level, 44 3-level and 20 4-level ACDF procedures, the average surgical time (minutes) was 68, 90, 118 and 141; length of stay (days) was 1, 1, 1.4, and 1.7; drain usage (%) was 1.3, 2.6, 13.6 and 10; and 30-day readmission rates (%) were 2.7, 3.9, 4.5, and 15, respectively. Combining the 1- and 2-level as a single group and 3- and 4-level as another cohort, the 3- and 4-level cohort had a significantly higher rate of drain usage and estimated blood loss (EBL) but there was not a difference in length-of-stay, complications or 30-day readmission rates. Conclusions Given the relative equivalent safety profile between 1- and 2-level as compared to 3- and 4-level ACDF, the proposed ERAS pathway can be applied to all patients, and not just restricted to 1-level or 2-level ACDF. Taking into account feasibility parameters as deduced from a review of institutional outcomes, this pathway can streamline same-day discharge and improve the patient experience. Its success will be predicated on an iterative improvement process deriving from optimal prospective outcome measurements.

Risk of Infection Associated with Transmucosal Placement of Instrumentation in Clean-Contaminated Field: Systematic Analysis.

Instability of the craniovertebral junction (CVJ) following odontoidectomy is relatively common. Traditionally, separate stage posterior atlantoaxial ± occipitocervical fusion is used for treatment. A transmucosal approach using a clean-contaminated route is associated with hypothetical risks of infectious complications. There is a paucity of information in the literature assessing the risk of surgical site infection (SSI) using the transmucosal approach for hardware placement. The authors conducted a literature search through PubMed identifying patients with pathology requiring transmucosal (i.e., transnasal or transoral) CVJ fixation. Studies that described 1) cases requiring a transmucosal approach and 2) associated infectious complications were included. Rates of SSIs, device removal, unplanned reoperation, and hardware failures were analyzed. Descriptive statistics and odds ratios (ORs) were used to compare complications. Nine studies with a total of 431 patients were identified. There were 4 (0.93%) superficial SSIs and 4 (0.93%) deep SSIs. In total, 1.86% of patients experienced SSI. There were 18 (4.18%) cases of unplanned reoperation, 4 (0.93%) related to SSI. Five (1.16%) patients required removal of their anterior fixation device, 4 (0.93%) related to SSI. ORs comparing our results with Medvedev et al's retrospective National Surgical Quality Improvement Program study assessing the risk associated with posterior cervical fixation showed no statistical difference between postoperative infection rates (OR = 0.72, P = 0.36). An extensive review of the literature found no evidence to suggest placement of spinal hardware via transmucosal corridor is associated with an increased risk of SSI.

Extra-abdominal Desmoid Tumor Mimicking Cervical Spine Schwannoma.

Extra-abdominal desmoid tumors (DTs) are rare tumors of apparent fibroblastic origin with unpredictable clinical behavior. Though histologically benign and slow growing, DTs can be proliferative, aggressive tumors, invading the surrounding areas. DTs located extra-abdominally are most commonly found in the extremities or proximal structures like the shoulders, chest wall, and neck. Spinal involvement is very rare. Here, we describe a case where an extra-abdominal DT mimicked a schwannoma in the posterior cervical spine. A 67-year-old female patient presented with acute neck and bilateral shoulder pain. After attempting conservative treatments with no symptomatic relief, a magnetic resonance imaging of the cervical spine was obtained, showing a paraspinal mass in the posterior elements from C2 to C4. The computed tomography guided needle biopsy showed rare spindle cells, suggestive of a spindle cell neoplasm, and complete surgical resection was performed. The pathology report was consistent with fibromatosis, leading to a final diagnosis of the extra-abdominal desmoid. This case demonstrates a rare presentation of an unusual tumor that often manifests with nonspecific symptoms or no symptoms at all.

Middle Cranial Fossa Approach to Repair Tegmen Defects with Autologous or Alloplastic Graft.

BACKGROUND: Temporal bone tegmen defects may be associated with cerebrospinal fluid (CSF) otorrhea. A variety of techniques have been used for repair. We report our experience with skull base reconstruction for tegmen defects using either autologous or alloplastic grafts. METHODS: A retrospective chart review was performed on patients with tegmen defects treated from 2007 to 2017 at the University Hospital in Columbia, Missouri, USA. Primary outcome measures were analyzed. RESULTS: Twenty-five patients were treated with a middle cranial fossa approach (median age 53, 88% females, median body mass index 34, median follow-up 9 months). Presenting symptoms included CSF leak (92%), hearing loss (44%), imbalance (12%), meningitis (12%), headache (4%), and tinnitus (4%). Most tegmen defects occurred spontaneously (84%) but cholesteatomas (4%), and trauma (12%) also were identified. Pre- and postoperative audiograms were available for 13 patients (52%); 7 (54%) showed objective improvement. Fourteen patients were repaired with autologous bone graft (56%), 7 with alloplastic grafts (28%), and 4 with temporalis fascia only (16%). All patients had resolution of CSF leak. Two patients (8%) suffered wound infections and 3 (12%) had facial and/or petrosal nerve complications. Use of alloplastic graft significantly shortened operative time (allopathic mean 180 minutes vs. autologous mean 208 minutes; P = 0.03). CONCLUSIONS: CSF otorrhea due to tegmen defects can be repaired via a middle fossa craniotomy using either an autologous or alloplastic graft with equivalent outcomes and efficacy, although alloplastic graft helps reduce operating time.

Modulators of cancer cell invasiveness.

Cell invasiveness is essential for cancer metastasis. Many proteins, and more recently also non-coding RNAs, particularly microRNAs (miRNAs), have been reported to affect the cell invasiveness of various cancers. There is an apparent gap between the high number of these macromolecules and the low number of signaling pathways experimentally verified to control cancer invasiveness. We have brought together these various proteins and RNAs because we could not find any publication that filled this important gap. We have noted 589 proteins, 28 miRNAs, and 1 long non-coding RNA that are reported to modulate invasiveness in cells of various cancers. Interestingly, 44 proteins enhance invasiveness in cells of some cancers, but suppress it in cells of others. Almost all of the proteins that show experimentally verified activation/inhibition effects on, or binding interactions with, each other are linked together in a single network, in a "hub-and-spoke" architecture. The accumulated data show trends that point to anticipated future results and highlight gaps in what is known about invasiveness signaling. Identification of cancer invasiveness signaling networks is important for combination and personalized targeted therapies of cancers.

Many new down- and up-regulatory signaling pathways, from known cancer progression suppressors to matrix metalloproteinases, differ widely in cells of various cancers.

Previously we detected new signaling pathways, some downregulatory and others upregulatory, from seven known suppressors of cancer progression to the expression of eight cancer-promoting matrix metalloproteinases (MMPs) in breast cancer cells. The goals of the present study were to test whether the preceding observations occur only in breast cancer cells and, if not, whether the same downregulatory and upregulatory signaling pathways are active in cells of other human cancers, focusing on activator protein-2alpha, E-cadherin, fibulin1D, interleukin 4, p16(INK4alpha), p53, PTEN, and RKIP, and on MMP1, MMP2, MMP7, MMP13, MMP14, MMP16, MMP19, and MMP25. To this end, in the present study we tested the effects of raising the cellular levels of wild-type copies of these known suppressors of cancer progression on the expression of these MMPs. This study yielded several unexpected results. We have detected 53 new signaling pathways in cells of prostate, brain, lung, ovarian and breast human cancers, with an abundance of signaling pathways as high as approximately 40% of the cancer progression regulator/MMP pairs tested in cells of prostate and breast cancers. Cells of various cancers differed widely and sequence-specifically in the identity of their signaling pathways, so that almost 90% of the pathways were different in cells from one cancer to another. In each of 18 out of 51 signaling pathways, a known suppressor of cancer progression stimulated, rather than inhibited, the expression of a cancer-promoting MMP. Ten signaling pathways were upregulatory in cells of some cancers and downregulatory in cells of other cancers.

Inflammation and cerebral vasospasm after subarachnoid hemorrhage.

Morbidity and mortality of patients with aneurysmal subarachnoid hemorrhage (aSAH) is significantly related to the development of chronic cerebral vasospasm. Despite extensive clinical and experimental research, the pathophysiology of the events that result in delayed arterial spasm is not fully understood. A review of the published literature on cerebral vasospasm that included but was not limited to all PubMed citations from 1951 to the present was performed. The findings suggest that leukocyte-endothelial cell interactions play a significant role in the pathophysiology of cerebral vasospasm and explain the clinical variability and time course of the disease. Experimental therapeutic targeting of the inflammatory response when timed correctly can prevent vasospasm, and supplementation of endothelial relaxation by nitric oxide-related therapies and other approaches could result in reversal of the arterial narrowing and improved outcomes in patients with aSAH.

Vein of Galen malformation.

A vein of Galen malformation is a rare intracranial vascular lesion affecting the pediatric population. Its poor prognosis has been significantly improved with the development of endovascular embolization. In this paper the authors review the developmental mechanisms, clinical pathophysiology, and the available data on the management and outcome of the disease.

Netrin-4 enhances angiogenesis and neurologic outcome after cerebral ischemia.

Functional recovery after cerebral ischemia is mediated by the regeneration of vascular networks and the restoration of synaptic architecture. Netrins have been implicated in neuronal pathfinding and angiogenesis. In this study, we investigated the expression of Netrin-4 and its putative receptors, deleted in colorectal cancer (DCC), Unc5A, and Unc5B after distal middle cerebral artery occlusion in mice. Netrin-4 protein was also administered intracerebroventricularly to examine its effect on angiogenesis and behavioral recovery. Netrin-4 protein was highly upregulated in the ischemic core as soon as 1 day after cerebral ischemia, with subsequent downregulation after 1 week. Its expression was limited to the area of blood-brain barrier damage and was seen on both blood vessels and astrocytic foot processes. Although there was not a significant upregulation of the putative Netrin-4 receptor Unc5A and Unc5B, there was a significant increase in expression of the DCC receptor on neuronal processes in the peri-infarct cortex. Intracerebroventricular administration of Netrin-4 into the ischemic brain increased blood vessel density, endothelial proliferation, and improved behavioral recovery at 1 week after stroke, but did not have an effect on blood-brain barrier permeability or infarct size. These findings suggest that Netrin-4 may improve poststroke functional recovery by enhancing blood vessel proliferation.

Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas.

OBJECTIVE: Anecdotal evidence suggests that radiosurgical ablation of parasagittal meningiomas may be associated with increased risk of subsequent edema. Potential predictors of postradiosurgical peritumoral edema, including parasagittal tumor location, tumor size, and treatment dose, were evaluated. METHODS: We retrospectively reviewed records of 102 patients with 111 supratentorial meningiomas treated with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS). A median marginal dose of 18.0 Gy (range, 11.3-25.0 Gy) was delivered in 1 to 5 sessions (fractions). Potential predictors of posttreatment symptomatic edema were evaluated using Fisher's exact test. RESULTS: Of the 102 patients followed for a mean of 20.9 months (range, 6-77 mo), 15 (14.7%) developed symptomatic edema after SRS. Nine of 31 with parasagittal meningiomas (29.0%) and 6 of 80 with nonparasagittal supratentorial meningiomas (7.5%) developed symptomatic edema (P = 0.0053). Compared with patients with meningiomas in nonmidline supratentorial locations, patients with parasagittal meningiomas were more than 4 times as likely to develop symptomatic edema after SRS (odds ratio, 4.1; 95% confidence interval, 1.5-11.5). The 6-, 12-, and 18-month actuarial rates of symptomatic edema development were significantly greater for patients with parasagittal meningiomas than for patients with nonparasagittal meningiomas (17.8 versus 1.3%, 25.4 versus 5.8%, and 35.2 versus 7.8%, respectively). CONCLUSION: Patients with parasagittal meningiomas are at greater risk of developing peritumoral symptomatic edema after SRS. Close follow-up after SRS may be particularly important in such patients. These results highlight the need to pursue strategies that could decrease the incidence of postradiosurgical edema in patients with parasagittal meningioma.

Thrombospondins 1 and 2 are necessary for synaptic plasticity and functional recovery after stroke.

Thrombospondins 1 and 2 (TSP-1/2) belong to a family of extracellular glycoproteins with angiostatic and synaptogenic properties. Although TSP-1/2 have been postulated to drive the resolution of postischemic angiogenesis, their role in synaptic and functional recovery is unknown. We investigated whether TSP-1/2 are necessary for synaptic and motor recovery after stroke. Focal ischemia was induced in 8- to 12-week-old wild-type (WT) and TSP-1/2 knockout (KO) mice by unilateral occlusion of the distal middle cerebral artery and the common carotid artery (CCA). Thrombospondins 1 and 2 increased after stroke, with both TSP-1 and TSP-2 colocalizing mostly to astrocytes. Wild-type and TSP-1/2 KO mice were compared in angiogenesis, synaptic density, axonal sprouting, infarct size, and functional recovery at different time points after stroke. Using the tongue protrusion test of motor function, we observed that TSP-1/2 KO mice exhibited significant deficit in their ability to recover function (P<0.05) compared with WT mice. No differences were found in infarct size and blood vessel density between the two groups after stroke. However, TSP-1/2 KO mice exhibited significant synaptic density and axonal sprouting deficits. Deficiency of TSP-1/2 leads to impaired recovery after stroke mainly due to the role of these proteins in synapse formation and axonal outgrowth.

Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model.

BACKGROUND AND PURPOSE: Intravascular delivery of neural stem cells (NSCs) after stroke has been limited by the low efficiency of transendothelial migration. Vascular cell adhesion molecule-1 is an endothelial adhesion molecule known to be upregulated early after stroke and is responsible for the firm adhesion of inflammatory cells expressing the surface integrin, CD49d. We hypothesize that enriching for NSCs that express CD49d and injecting them into the carotid artery would improve targeted cell delivery to the injured brain. METHODS: Mouse NSCs were analyzed for the expression of CD49d by fluorescence activated cell sorting. A CD49d-enriched (CD49d(+)) (>95%) and -depleted (CD49d(-); <5%) NSC population was obtained by cell sorting. C57/Bl6 mice underwent left-sided hypoxia-ischemia surgery and were assigned to receive 3 x 10(5) CD49d(+), CD49d(-) NSCs, or vehicle injection into the left common carotid artery 48 hours after stroke. Behavioral recovery was measured using a rotarod for 2 weeks after cell injection. RESULTS: Fluorescence activated cell sorting analysis revealed 25% CD49d(+) NSCs. In a static adhesion assay, NSCs adhered to vascular cell adhesion molecule-1 in a dose-dependent manner. Significantly more NSCs were found in the cortex, the hippocampus, and the subventricular zone in the ischemic hemisphere in animals receiving CD49d(+) NSCs as compared with CD49d(-) NSCs (P<0.05). Animals treated with CD49d(+) cells showed a significantly better behavioral recovery as compared with CD49d(-) and vehicle-treated animals. CONCLUSIONS: We show that enrichment of NSCs by fluorescence activated cell sorting for the surface integrin, CD49d, and intracarotid delivery promotes cell homing to the area of stroke in mice and improves behavioral recovery.