Factors influencing cage subsidence in anterior cervical corpectomy and discectomy: a systematic review.

PURPOSE: Various factors have been examined in relation to cage subsidence risk, including cage material, cage geometry, bone mineral density, device type, surgical level, bone graft, and patient age. The present study aims to compare and synthesize the literature of both clinical and biomechanical studies to evaluate and present the factors associated with cage subsidence. METHODS: A comprehensive search of the literature from January 2003 to December 2021 was conducted using the PubMed and ScienceDirect databases by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following the screening for inclusion and exclusion criteria, a total of 49 clinical studies were included. Correlations between clinical and biomechanical studies are also discussed. RESULTS: Patients treated with the cage and plate combination had a lower subsidence rate than patients with the stand-alone cage. Overall, Polyetheretherketone material was shown to have a lower subsidence rate than titanium and other materials. The subsidence rate was also higher when the surgery was performed at levels C5-C7 than at levels C2-C5. No significant correlation was found between age and cage subsidence clinically. CONCLUSIONS: Cage subsidence increases the stress on the anterior fixation system and may cause biomechanical instability. Severe cage subsidence decreases the Cobb angle and intervertebral height, which may cause destabilization of the implant system, such as screw/plate loosening or breakage of the screw/plate. Various factors have been shown to influence the risk of cage subsidence. Examining clinical research alongside biomechanical studies offers a more comprehensive understanding of the subject.

A New Method to Evaluate Pressure Distribution Using a 3D-Printed C2-C3 Cervical Spine Model with an Embedded Sensor Array.

Cervical degenerative disc diseases such as myelopathy and radiculopathy often require conventional treatments like artificial cervical disc replacement or anterior cervical discectomy and fusion (ACDF). When designing a medical device, like the stand-alone cage, there are many design inputs to consider. However, the precise biomechanics of the force between the vertebrae and implanted devices under certain conditions require further investigation. In this study, a new method was developed to evaluate the pressure between the vertebrae and implanted devices by embedding a sensor array into a 3D-printed C2-C3 cervical spine. The 3D-printed cervical spine model was subjected to a range of axial loads while under flexion, extension, bending and compression conditions. Cables were used for the application of a preload and a robotic arm was used to recreate the natural spine motions (flexion, extension, and bending). To verify and predict the total pressure between the vertebrae and the implanted devices, a 3D finite element (FE) numerical mathematical model was developed. A preload was represented by applying 22 N of force on each of the anterior tubercles for the C2 vertebra. The results of this study suggest that the sensor is useful in identifying static pressure. The pressure with the robot arm was verified from the FE results under all conditions. This study indicates that the sensor array has promising potential to reduce the trial and error with implants for various surgical procedures, including multi-level artificial cervical disk replacement and ACDF, which may help clinicians to reduce pain, suffering, and costly follow-up procedures.

Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability.

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of the Oct3/4 network associated with tumor initiation and metastasis. In the triple negative breast cancer cell line (MDA-MB-231) stably transfected with human Oct3/4-GFP, differentially expressed genes (DEGs) were identified using qPCR and microarray, and the resistance to paclitaxel was assessed using an MTS assay. The tumor-seeding potential in immunocompromised (NOD-SCID) mice and DEGs in the tumors were also assessed along with the intra-tumor (CD44+/CD24-) expression using flow cytometry. Unlike 2-D cultures, the Oct3/4-GFP expression was homogenous and stable in 3-D mammospheres developed from BCSCs. A total of 25 DEGs including Gata6, FoxA2, Sall4, Zic2, H2afJ, Stc1 and Bmi1 were identified in Oct3/4 activated cells coupled with a significantly increased resistance to paclitaxel. In mice, the higher Oct3/4 expression in tumors correlated with enhanced tumorigenic potential and aggressive growth, with metastatic lesions showing a >5-fold upregulation of DEGs compared to orthotopic tumors and variability in different tissues with the highest modulation in the brain. Serially re-implanting tumors in mice as a model of recurrence and metastasis highlighted the sustained upregulation of Sall4, c-Myc, Mmp1, Mmp9 and Dkk1 genes in metastatic lesions with a 2-fold higher expression of stem cell markers (CD44+/CD24-). Thus, Oct3/4 transcriptome may drive the differentiation and maintenance of BCSCs, promoting their tumorigenic potential, metastasis and resistance to drugs such as paclitaxel with tissue-specific heterogeneity.

Gender differences in Alzheimer's may be associated with TLR4-LYN expression in damage associated microglia and neuronal phagocytosis.

The role of Aß plaques and neurofibrillary tangles in Alzheimer's disease (AD) pathogenesis have recently come into question due to failure of many pharmaceutical agents targeting these deposits and detection of these misfolded proteins in normal human brains. Therefore, we investigated correlations between microglial activation and toll like receptor 4 (TLR4) and Lck/Yes novel tyrosine (LYN) kinase signaling in an AD mouse model. In this study, we used 5-6-month-old 5XFAD and wild type (WT) male and female mice. Immunohistochemistry (IHC) and flow cytometry (FC) were performed on their brains. Cognitive performance was assessed with the Barnes-Maze. IHC showed more Ab aggregation in microglia of female 5XFAD mice compared to their male counterparts. Increased co-localization of microglial TLR4 and LYN was also observed in AD more than WT and females more than males. IHC also suggests microglial phagocytosis of neurons in AD mice, which is supported by FC data. Our FC data also support the involvement of disease associated microglia (DAMs) in this process based on cytokine secretion. Cognitive assessment by the Barnes maze showed 5XFAD females performed worse than males. In this study, we investigated the relationship between microglial TLR4 and LYN kinase in 5XFAD male and females. Our data reveals a correlation between microglial TLR4 and LYN co-localization and AD pathogenesis, more in females than males. Targeting microglial TLR4 and Lyn in DAMs may offer new therapeutic opportunities in the treatment of AD.

An overview on microglial origin, distribution, and phenotype in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease that is responsible for about one-third of dementia cases worldwide. It is believed that AD is initiated with the deposition of Ab plaques in the brain. Genetic studies have shown that a high number of AD risk genes are expressed by microglia, the resident macrophages of brain. Common mode of action by microglia cells is neuroinflammation and phagocytosis. Moreover, it has been discovered that inflammatory marker levels are increased in AD patients. Recent studies advocate that neuroinflammation plays a major role in AD progression. Microglia have different activation profiles depending on the region of brain and stimuli. In different activation, profile microglia can generate either pro-inflammatory or anti-inflammatory responses. Microglia defend brain cells from pathogens and respond to injuries; also, microglia can lead to neuronal death along the way. In this review, we will bring the different roles played by microglia and microglia-related genes in the progression of AD.

Microglial TLR4 is Critical for Neuronal Injury and Cognitive Dysfunction in Subarachnoid Hemorrhage.

BACKGROUND: Toll-like receptor 4 (TLR4) activation causes excessive production of proinflammatory mediators and an increased expression of costimulatory molecules that leads to neuroinflammation after subarachnoid hemorrhage (SAH). Although TLR4-mediated inflammatory pathways have long been studied in neuroinflammation, the specific glia implicated in initiation and propagation of neuroinflammation in SAH have not been well elucidated. In this study, we investigated the involvement of glial TLR4 including microglia and astrocytes in brain damage and poor neurological outcome. METHODS: In this study, global TLR4 knockout, cell-specific TLR4 knockout, and floxxed control male and female mice were used. The mice were injected with 60 µl autologous blood near the mesencephalon to induce SAH; animals were euthanized on postoperative day 7 for immunohistochemistry of glia and apoptotic cells. Microglial morphology was evaluated by using immunofluorescence density quantification to determine correlations between morphology and neuroinflammation. Microglial depletion was accomplished with the intracerebroventricular administration of clodronate liposomes. Cognitive function was assessed with Barnes maze. RESULTS: On postoperative day 7 after SAH induction, neuronal apoptosis was markedly reduced in the clodronate liposome group compared with phosphate-buffered saline control liposomes, and cognitive performance in the clodronate group was improved, as well. Differences in microglial activation, assessed by morphometric analysis, and neuronal apoptosis were significantly greater in wildtype knockouts compared with cell-specific and global TLR4 knockouts. The mice lacking TLR4 on astrocytes and neurons showed no differences compared with wildtype mice on any end points. CONCLUSIONS: Our data suggest that microglial depletion with the intracerebroventricular administration of clodronate can improve the cognitive function in an SAH mouse model, and TLR4 is critical for microglial activation and neuronal injury. Only microglial TLR4 is necessary for brain damage and poor cognitive outcome rather than astrocyte or neuronal TLR4. Thus, microglial TLR4 could be a potent therapeutic target to treat SAH-associated neuronal injury and protect against cognitive dysfunction.

Robotic Replica of a Human Spine Uses Soft Magnetic Sensor Array to Forecast Intervertebral Loads and Posture after Surgery.

Cervical disc implants are conventional surgical treatments for patients with degenerative disc disease, such as cervical myelopathy and radiculopathy. However, the surgeon still must determine the candidacy of cervical disc implants mainly from the findings of diagnostic imaging studies, which can sometimes lead to complications and implant failure. To help address these problems, a new approach was developed to enable surgeons to preview the post-operative effects of an artificial disc implant in a patient-specific fashion prior to surgery. To that end, a robotic replica of a person's spine was 3D printed, modified to include an artificial disc implant, and outfitted with a soft magnetic sensor array. The aims of this study are threefold: first, to evaluate the potential of a soft magnetic sensor array to detect the location and amplitude of applied loads; second, to use the soft magnetic sensor array in a 3D printed human spine replica to distinguish between five different robotically actuated postures; and third, to compare the efficacy of four different machine learning algorithms to classify the loads, amplitudes, and postures obtained from the first and second aims. Benchtop experiments showed that the soft magnetic sensor array was capable of precisely detecting the location and amplitude of forces, which were successfully classified by four different machine learning algorithms that were compared for their capabilities: Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Random Forest (RF), and Artificial Neural Network (ANN). In particular, the RF and ANN algorithms were able to classify locations of loads applied 3.25 mm apart with 98.39% ± 1.50% and 98.05% ± 1.56% accuracies, respectively. Furthermore, the ANN had an accuracy of 94.46% ± 2.84% to classify the location that a 10 g load was applied. The artificial disc-implanted spine replica was subjected to flexion and extension by a robotic arm. Five different postures of the spine were successfully classified with 100% ± 0.0% accuracy with the ANN using the soft magnetic sensor array. All results indicated that the magnetic sensor array has promising potential to generate data prior to invasive surgeries that could be utilized to preoperatively assess the suitability of a particular intervention for specific patients and to potentially assist the postoperative care of people with cervical disc implants.

Cerebrospinal Fluid and Hydrocephalus: Physiology, Diagnosis, and Treatment.

BACKGROUND: Cerebrospinal fluid (CSF) is found around and inside the brain and vertebral column. CSF plays a crucial role in the protection and homeostasis of neural tissue. METHODS: Key points on the physiology of CSF as well as the diagnostic and treatment options for hydrocephalus are discussed. RESULTS: Understanding the fundamentals of the production, absorption, dynamics, and pathophysiology of CSF is crucial for addressing hydrocephalus. Shunts and endoscopic third ventriculostomy have changed the therapeutic landscape of hydrocephalus. CONCLUSIONS: The treatment of hydrocephalus in adults and children represents a large part of everyday practice for the neurologist, both in benign cases and cancer-related diagnoses.

Surgical Treatment for Leptomeningeal Disease.

BACKGROUND: Advancements in cancer treatment have led to more cases of leptomeningeal disease, which requires a multimodal approach. METHODS: Treatment modalities are reviewed from a neurosurgical standpoint, focusing on intrathecal chemotherapy and shunting devices. Potential complications and how to avoid them are discussed. RESULTS: The Ommaya reservoir and the chemoport are used for administering intrathecal chemotherapy. Use of ventriculo-lumbar perfusion can efficiently deliver chemotherapeutic agents and improve intracerebral pressure. Shunting systems, in conjunction with all of their variations, address the challenge of hydrocephalus in leptomeningeal carcinomatosis. Misplaced catheters, malfunction of the system, and shunt-related infections are known complications of treatment. CONCLUSIONS: From an oncological perspective, the surgical treatment for leptomeningeal disease is limited; however, neurosurgery can be used to aid in the administration of chemotherapy and address the issue of hydrocephalus. Minimizing surgical complications is important in this sensitive patient population.

Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells.

Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma.

Resection of the First Rib With Preservation of the T1 Nerve Root in Pancoast Tumors of the Lung.

BACKGROUND: Surgical outcomes for Pancoast (superior sulcus) tumors of the lung have significantly changed during the last few decades and have improved with use of curative-intent surgery by utilizing en bloc complete resections. METHODS: A retrospective analysis was conducted of 11 selected patients treated at Moffitt Cancer Center from 2007 to 2016. Data from patient records were collected and analyzed. RESULTS: All 11 patients with a Pancoast tumor involving the first rib had their T1 root preserved at surgery. In 10 patients (90.9%), the tumor was removed en bloc. Clear margins of resection were documented in 4 cases (36.0%). No patient developed postoperative hand weakness, but 3 patients (27.3%) had minor postoperative complications, including air leak, chylothorax, and pericardial effusion. One iatrogenic injury to the subclavian artery was reported during surgery; the injury was subsequently repaired. No operative mortality was reported. CONCLUSIONS: Radical resection of Pancoast tumors is considered to be safe, and preserving the T1 nerve root provides more favorable, functional outcomes.

Central Nervous System Cancers, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas.

Robotics in Neurosurgery: Evolution, Current Challenges, and Compromises.

BACKGROUND: Advances in technology have pushed the boundaries of neurosurgery. Surgeons play a major role in the neurosurgical field, but robotic systems challenge the current status quo. Robotic-assisted surgery has revolutionized several surgical fields, yet robotic-assisted neurosurgery is limited by available technology. METHODS: The literature on the current robotic systems in neurosurgery and the challenges and compromises of robotic design are reviewed and discussed. RESULTS: Several robotic systems are currently in use, but the application of these systems is limited in the field of neurosurgery. Most robotic systems are suited to assist in stereotactic procedures. Current research and development teams focus on robotic-assisted microsurgery and minimally invasive surgery. The tasks of miniaturizing the current tools and maximizing control challenge manufacturers and hinder progress. Furthermore, loss of haptic feedback, proprioception, and visualization increase the time it takes for users to master robotic systems. CONCLUSIONS: Robotic-assisted surgery is a promising field in neurosurgery, but improvements and breakthroughs in minimally invasive and endoscopic robotic-assisted surgical systems must occur before robotic assistance becomes commonplace in the neurosurgical field.

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.

Spinal tumor surgery: management and the avoidance of complications.

BACKGROUND: Complication avoidance is paramount to the success of any surgical procedure. In the case of spine tumor surgery, the risk of complications is increased because of the primary disease process and the radiotherapy and chemotherapeutics used to treat the disease. If complications do occur, then life-saving adjuvant treatment must be delayed or withheld until the issue is resolved, potentially impacting overall disease control. METHODS: We reviewed the literature and our own best practices to provide recommendations on complication avoidance as well as the management of complications that may occur. Appropriate workup of suspected complications and treatment algorithms are also discussed. RESULTS: Appropriate patient selection and a multidisciplinary workup are imperative in the setting of spinal tumors. Intraoperative complications may be avoided by employing proper surgical technique and an understanding of the pathological changes in anatomy. Major postoperative issues include wound complications and spinal reconstruction failure. Preoperative surgical planning must include postoperative reconstruction. Patients undergoing spinal tumor resection should be closely monitored for local tumor recurrence, recurrence along the biopsy tract, and for distant metastatic disease. Any suspected recurrence should be closely watched, biopsied if necessary, and promptly treated. CONCLUSIONS: Because patients with spinal tumors are normally treated with a multidisciplinary approach, emphasis should be placed on the recognition of surgical complications beyond the surgical setting.

Primary spine tumors: diagnosis and treatment.

BACKGROUND: Primary tumors are rare and those localized to a single location offer the potential for cure. To achieve this, early recognition of the primary tumor and proper workup and treatment are essential. METHODS: The authors reviewed the literature and best practices to provide recommendations on primary spine tumor treatment. Appropriate workup of primary spine tumors and treatment algorithms are also discussed. RESULTS: Patients suspected of a primary spine tumor should undergo fine-needle aspirate biopsy following consultation with the surgical team to ensure the biopsy tract is surgically resectable should the need arise. Once pathology is confirmed, metastatic workup should be performed to guide the level of treatment. If a localized lesion with poor radiation and chemotherapeutic response is diagnosed, then en bloc resection may be required for cure. If en bloc resection is not feasible or metastatic lesions are present, then radiation and medical oncology specialists must work in conjunction with the surgical team to determine the best treatment options. CONCLUSIONS: Patients with suspected primary tumors of the spine should be treated in a multidisciplinary fashion from the outset. With thoughtful management, these lesions offer the opportunity for surgical cure.

Management of locally advanced pancoast (superior sulcus) tumors with spine involvement.

BACKGROUND: The preferred treatment for locally aggressive lung cancers is triple modality therapy with concurrent and induction chemotherapy with radiation therapy followed by surgery. Patients with locally advanced T4 Pancoast tumors with spine involvement, without mediastinal N2 lymph node involvement and without distant metastases, are appropriate candidates for complete resection with subsequent spine reconstruction. This review addresses the questions of whether triple modality therapy with complete en bloc resection of locally advanced Pancoast tumors offers an advantage in terms of overall survival and complication rates compared with other therapeutic modalities or therapies with incomplete resection. METHODS: A comprehensive literature search was conducted using common medical databases. Inclusion and exclusion criteria for the articles were prospectively defined. The articles were independently reviewed and a consensus decision was made about each article. Selected papers were graded by level of evidence. RESULTS: A total of 1,001 abstracts and 93 articles fulfilled the criteria; from these studies, 14 were included in this systematic review. No level 1 study was found in this search. Four level 2 studies and 10 level 3 retrospective case series were found. The overall 5-year survival rate reported in these studies ranged from 37% to 59% and the mortality rate ranged from 0% to 6.9%. CONCLUSIONS: Evidence suggests that triple modality therapy with complete resection of locally advanced Pancoast tumors with involvement of the spine offers an advantage over other therapeutic modalities or therapies with incomplete resections.

Controversial issues in kyphoplasty and vertebroplasty in malignant vertebral fractures.

BACKGROUND: Kyphoplasty (KP) and vertebroplasty (VP) have been successfully employed in the treatment of pathological vertebral fractures. METHODS: A critical review of the medical literature was performed and controversial issues were analyzed. RESULTS: Evidence supports KP as the treatment of choice to control fracture pain and the possible restoration of sagittal balance, provided that no overt instability or myelopathy is present, the fracture is painful and other pain generators have been excluded, and positive radiological findings are present. Unilateral procedures yield similar results to bilateral ones and should be pursued whenever feasible. Biopsy should be routinely performed and 3 to 4 levels may be augmented in a single operation. Higher cement filling appears to yield better results. Radiotherapy is complementary with KP and VP but must be individualized. CONCLUSIONS: In cases of painful cancer fractures, if overt instability or myelopathy is not present, unilateral KP should be pursued, whenever feasible, followed by radiotherapy. The technological advances in hardware and biomaterials, as well as combining KP with other modalities, will help ensure a safe and more effective procedure. Address.

Palliative strategies for the management of primary and metastatic spinal tumors.

BACKGROUND: Technological advances during the last few decades have improved the success rate of surgery for the treatment of malignant spinal tumors. Nonetheless, many patients present with widespread tumor burden and minimal life expectancy, which excludes them from being surgical candidates. For these patients, palliative management is recommended. METHODS: The authors reviewed prospective and retrospective clinical studies as well as case series regarding palliative treatments for primary and metastatic spinal tumors. RESULTS: Analgesics, ranging from nonopioids to strong opioids, may be used depending on the degree of pain. Steroids may also improve pain relief, although they are associated with a number of adverse events. Vertebroplasty and kyphoplasty are conservative treatments with high rates of pain relief and vertebral body stabilization. Radiotherapy is the gold standard for palliative management, with approximately 60% of patients experiencing a decrease in tumor-related spinal pain and up to 35% experiencing complete relief. Stereotactic radiosurgery delivers high doses of radiation to patients to provide pain relief while also sparing delicate anatomical structures. CONCLUSION: Palliative management of spinal tumors is diverse. Analgesics may be used in conjunction with radiotherapy and/or kyphoplasty or vertebroplasty to offer pain relief.

Spinal neoplastic instability: biomechanics and current management options.

BACKGROUND: Often the spine is afflicted from primary or metastatic neoplastic disease, which can lead to instability. Instability can cause deformity, pain, and spinal cord compression and is an indication for surgery. Although overt instability is uniformly agreed upon, it is sometimes difficult for specialists to agree on subtle degrees of instability due to lack of objective criteria. METHODS: In this article, treatment options and the spine instability neoplastic system are discussed and the neoplastic instability literature is reviewed. RESULTS: The Spinal Instability Neoplastic Score helps specialists determine whether instability is present and when surgery may be indicated. However, other parameters such as spinal cord compression and extent of disease dictate whether surgery is the most appropriate option. A wide range of fusion techniques exists, each one tailored to the location of the lesion and goals for surgery. CONCLUSIONS: To optimize results, expert knowledge on the techniques and patient selection is of importance. Furthermore, a multidisciplinary approach is required because treatment of neoplastic disease is multimodal.