Application of the NSE score (Neurology-Stability-Epidural compression assessment) to establish the need for surgery in spinal metastases of elderly patients: a multicenter investigation.

PURPOSE: This retropective multicentric study aims to investigate the clinical applicability of the NSE score in the elderly, to verify the role of this tool as an easy help for decision making also for this class of patients. METHODS: All elderly patients (> 65 years) suffering from spinal metastases undergoing surgical or non-surgical treatment at the authors' Institutions between 2015 and 2022 were recruited. An agreement group (AG) and non-agreement group (NAG) were identified accordingly to the agreement between the NSE score indication and the performed treatment. Neurological status and axial pain were evaluated for both groups at follow-up (3 and 6 months). The same analysis was conducted specifically grouping patients older than 75 years. RESULTS: A strong association with improvement or preservation of clinical status (p < 0.001) at follow-up was obtained in AG. The association was not statistically significant in NAG at the 3-month follow-up (p 1.00 and 0.07 respectively) and at 6 months (p 0.293 and 0.09 respectively). The group of patients over 75 years old showed similar results in terms of statistical association between the agreement group and better outcomes. CONCLUSION: Far from the need or the aim to build dogmatic algorithms, the goal of preserving a proper performance status plays a key role in a modern oncological management: functional outcomes of the multicentric study group showed that the NSE score represents a reliable tool to establish the need for surgery also for elderly patients.

Extreme Lateral Interbody Fusion (XLIF) with Lateral Modular Plate Fixation: Preliminary Report on Clinical and Radiological Outcomes.

The lateral transpsoas approach (extreme lateral interbody fusion, or XLIF) allows surgeons to use various lordotic cage sizes to help restore intervertebral disk height, correct sagittal alignment, and improve fusion rates. The use of standalone devices has consistently raised doubts due to the high risk of complications and inadequate functional recovery that a circumferential arthrodesis can support. The recent introduction of a novel XLIF cage with adapted lateral plate fixation (XLPF) may further enhance the structural rigidity, consolidating the cage and plate into a singular modular entity. Nine patients from our surgical centers underwent a procedure of 1-level XLIF with XLPF in selected cases. We observed that XLPF does not extend the intraoperative footprint and provides immediate rigidity to the anterior column without any additional risk of complications and with minimal increased time compared to the traditional cage implant procedure. Although it has been shown that the use of interbody fusion cages with supplemental posterior fixation improves stabilization in all directions, the technique of standalone lateral cages may also have a place in spine surgery in that the stability may be sufficient in selected cases, such as junctional syndrome and in some forms of degenerative scoliosis.

Spinal epidural capillary hemangioma: case report and review of the literature.

BACKGROUND: Almost all of the epidural hemangiomas reported are cavernous hemangiomas. Purely extradural spinal capillary hemangiomas are very rare. Capillary hemangiomas are hamartomatous malformations that result from proliferations of vascular endothelial cells. Only ten cases have been reported in the English literature, treated with surgical excision. CASE DESCRIPTION: A case of a dorsal extradural spinal capillary hemangioma is described. A total surgical removal has been performed after spinal angiography and embolization. Complete surgical removal should always be the goal in these lesions. Embolization did not show to reduce bleeding during the surgical procedure in this case.

Posterior arch reconstruction in cervical surgery to restore the global biomechanics of the Atlas: a technical note.

The posterior arch of the atlas is usually not considered one of the main stabilizers of the cranio-cervical junction, allowing surgeons to its removal when needed with a relative certainty to preserve the stability of the atlo-axial segment. However, these considerations do not reflect the importance to examine the integrity of the posterior arch in the whole biomechanics of the atlas. Authors like Gebauer and Panjabi revealed, respectively in experimental and clinical conditions, how the atlas responds to an axial loading force, proving that the whole atlas is involved into horizontal conversion of axial forces and providing evidence supporting the preservation of the posterior arch. Other authors evaluated the risk for anterior arch fracture following C1 laminectomy. In this technical note three different techniques of posterior atlas arch reconstruction after surgical iatrogenic disruption are presented, considering both neoplastic and degenerative disease.

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review.

Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.

Systematic Review on Tumor Microenvironment in Glial Neoplasm: From Understanding Pathogenesis to Future Therapeutic Perspectives.

Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.

Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review.

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords "nerve regeneration", "stem cells", "peripheral nerve injury", "rat", and "human" were used. Additionally, a "MeSH" research was performed in PubMed using the terms "stem cells" and "nerve regeneration". The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.

Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages.

Titanium is one of the most frequently used materials in bone regeneration due to its good biocompatibility, excellent mechanical properties, and great osteogenic performance. However, osseointegration with host tissue is often not definite, which may cause implant failure at times. The present study investigates the capacity of the mesenchymal stem cell (MSC)-secretome, formulated as a ready-to-use and freeze-dried medicinal product (the Lyosecretome), to promote the osteoinductive and osteoconductive properties of titanium cages. In vitro tests were conducted using adipose tissue-derived MSCs seeded on titanium cages with or without Lyosecretome. After 14 days, in the presence of Lyosecretome, significant cell proliferation improvement was observed. Scanning electron microscopy revealed the cytocompatibility of titanium cages: the seeded MSCs showed a spread morphology and an initial formation of filopodia. After 7 days, in the presence of Lyosecretome, more frequent and complex cellular processes forming bridges across the porous surface of the scaffold were revealed. Also, after 14 and 28 days of culturing in osteogenic medium, the amount of mineralized matrix detected by alizarin red was significantly higher when Lyosecretome was used. Finally, improved osteogenesis with Lyosecretome was confirmed by confocal analysis after 28 and 56 days of treatment, and demonstrating the production by osteoblast-differentiated MSCs of osteocalcin, a specific bone matrix protein.

Comorbidity of Cervical Spondylogenic Myelopathy and Amyotrophic Lateral Sclerosis: When Electromyography Makes the Difference in Diagnosis.

Cervical spondylogenic myelopathy (CSM) represents a common differential diagnosis for spinal onset Amyotrophic Lateral Sclerosis (ALS). Identifying occurrence of ALS in patients with CSM may be challenging. We evaluated the accuracy of Awaji criteria in the diagnosis of ALS in a cohort of patients with CSM. We screened all patients attending Turin ALS Center during the 2006-2018 period. We selected only patients for whom cervical cord MRI showed radiological signs of CSM. All patients underwent electromyography (EMG), and Awaji criteria were used for diagnosis of clinically probable ALS. All patients were followed up clinically for at least 6 months, and ALS diagnosis was eventually confirmed according to El-Escorial revised criteria, based on disease progression. Of 2,059 patients screened, in 42 cases, MRI showed signs of CSM; CSM incidence and prevalence risks were 0.16 and 2.04%, respectively. Based on clinical progression, 72.7% of patients were diagnosed as CSM and 27.3% as CSM + ALS. At EMG 6 (18.2%) patients fulfilled the criteria for ALS, 5 of them (83.3%) during clinical follow-up were diagnosed as clinical definite ALS + CSM. Accuracy of Awaji criteria in diagnosing ALS was good (AUC = 0.757, p = 0.03). Sensitivity and specificity of Awaji criteria were, respectively, 55.6 and 95.8%. Positive predictive value was 83.3%, while negative predictive value was 85.2%. CSM-ALS comorbidity is a relatively common problem in clinical practice. To better choose patients who could benefit from surgery, EMG should be performed in CSM patients, due to its good accuracy in recognizing ALS.

Transpedicular 3D endoscope-assisted thoracic corpectomy for separation surgery in spinal metastases: feasibility of the technique and preliminary results of a promising experience.

Surgery for spinal metastases has undergone multiple transformations in terms of surgical technique. The need for a more aggressive surgical strategy for local control of the disease, given the advances in radiosurgery and immunotherapy, has met the incorporation of many different technological adjuncts. Separation surgery has become one of the main targets to achieve for surgeons in the treatment of spinal metastases. In this paper a prospective series of 3D endoscope-assisted transpedicular thoracic corpectomies is described. Adult patients with a diagnosis of single-level thoracic metastases requiring surgery for epidural compression were included. Data recorded for each case concerned patient demographics, surgical technique, clinical, radiological and surgical data, intra- and postoperative complications, follow-up. The goal of this study was to verify the achievement of separation surgery with this technique, while confirming the safety and feasibility of the procedure. A total number of nine patients were treated from January to April 2019 with a 3D endoscope-assisted procedure. A circumferential bilateral decompression was achieved in seven cases, while monolateral in the other two. A proper separation between the tumor and the spinal cord was achieved in all cases as confirmed by imaging. Axial pain always improved after the procedure as well as neurological functions, when compromised before surgery. No intra-operative and postoperative complications were recorded. Mean hospital stay was 4 days after surgery with early mobilization. At last follow-up no local recurrences were registered. According to preliminary results, the transpedicular 3D endoscope-assisted approach for corpectomies appeared to be a safe and effective technique to achieve proper circumferential decompression and valid separation surgery in thoracic metastases, potentially decreasing the need for costotransversectomy.

Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

OBJECTIVE: Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. METHODS: Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. RESULTS: Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76-0.81). CONCLUSIONS: The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target.

The neurotrophic tropomyosin receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) code for three transmembrane high-affinity tyrosine-kinase receptors for nerve growth factors (TRK-A, TRK-B, and TRK-C) which are mainly involved in nervous system development. Loss of function alterations in these genes can lead to nervous system development problems; conversely, activating alterations harbor oncogenic potential, promoting cell proliferation/survival and tumorigenesis. Chromosomal rearrangements are the most clinically relevant alterations of pathological NTRK activation, leading to constitutionally active chimeric receptors. NTRK fusions have been detected with extremely variable frequencies in many pediatric and adult cancer types, including central nervous system (CNS) tumors. These alterations can be detected by different laboratory assays (e.g., immunohistochemistry, FISH, sequencing), but each of these approaches has specific advantages and limitations which must be taken into account for an appropriate use in diagnostics or research. Moreover, therapeutic targeting of this molecular marker recently showed extreme efficacy. Considering the overall lack of effective treatments for brain neoplasms, it is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.

The Targeted Therapies Era Beyond the Surgical Point of View: What Spine Surgeons Should Know Before Approaching Spinal Metastases.

In the last few years, the treatment of spinal metastases has significantly changed. This is due to the advancements in surgical technique, radiotherapy, and chemotherapy which have enriched the multidisciplinary management. Above all, the field of molecular biology of tumors is in continuous and prosperous evolution. In this review, the molecular markers and new approaches that have radically modified the chemotherapeutic strategy of the most common metastatic neoplasms will be examined together with clinical and surgical implications. The experience and skills of several different medical professionals are mandatory: an interdisciplinary oncology team represents the winning strategy in the treatment of patients with spinal metastases.

Intraoperative neurophysiological monitoring during spinal surgery: technical review in open and minimally invasive approaches.

Neurophysiological monitoring is of undoubted value for the intraoperative safety of neurosurgical procedures. Widely developed and used for cranial surgery, it is equally as effective, though perhaps less commonly employed, for spinal pathology. The most frequently used techniques for intraoperative monitoring during spinal surgery include somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs) and electromyography, which can either be spontaneous free-running (sEMG) or triggered (tEMG). The knowledge of the benefits and limitations of each modality is essential in optimising the value of intraoperative monitoring during spinal procedures. This review will analyse the single techniques, their anatomical and physiological basis, their use in spinal surgery as reliable indicators of functional injury, their limits and their application to specific procedures in minimally invasive surgery, such as the lateral transpsoas access for interbody fusion and the divergent trajectory for cortico-pedicular screws. In these particular techniques, because of reduced visual exposure, neuromonitoring is indeed essential to exploit the full potential of minimally invasive surgery, while avoiding damage to nervous structures.

Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy

Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives.

Tumor location and patient age predict biological signatures of high-grade gliomas.

Prognostic factors for high-grade gliomas include patient age, IDH1 mutation, MGMT methylation, and Ki67 value. We assessed the predictive role of topographic location of gliomas for their biological signatures. Collecting all neuroradiological and histological data of patients with histologically proven HGG, we performed a retrospective monocentric study. A predictive value of frontal location for a lower Ki67 value (especially in the left hemisphere) and mutation of IDH1 (especially in the right hemisphere) was found. Temporal location was predictive for IDH1 wild-type. Involvement of the parietal lobe was found to be predictive of methylated MGMT, while insular lobe involvement predicted an unmethylated MGMT. There was no statistically significant difference of IDH1 mutation and MGMT methylation between left and right sides.

Cortical bone trajectory screws for circumferential arthrodesis in lumbar degenerative spine: clinical and radiological outcomes of 101 cases.

PURPOSE: The use of cortical bone trajectory (CBT) pedicle screws for circumferential interbody fusion represents a viable alternative for single-level procedure with reduced invasiveness and less tissue destruction than the traditional technique. In addition, CBT screws have a potentially stronger pullout strength because of the greater amount of cortical bone intercepted. Only few series exist evaluating clinical and radiological outcomes of CBT screws. METHODS: This is a retrospective cohort study. All patients that underwent circumferential lumbar interbody fusion with CBT screws in our institution from 2014 to 2017 were reviewed. Patient demographics, clinical outcome with visual analogue scale (VAS) and Oswestry Disability Index (ODI), radiological data such as fusion, lordosis and muscle trauma, operative blood loss, hospital stay and use of fluoroscopy were evaluated. RESULTS: A total of 101 patients undergoing CBT-arthrodesis for degenerative lumbo-sacral disease were reviewed. Mean procedural time was 187 min. The mean operative blood loss and X-ray dose per procedure was 383 ml and 1.60 mg cm2, respectively. The mean hospital stay was 3.47 days. The mean follow-up was 18.23 months. Mean lordosis increment at the treated level was 4.2°. When the follow-up was longer than 12 months (53% of patients), fusion was obtained in 94% of cases. Mean ODI and VAS index improved with statistical significance. CONCLUSIONS: This is to our knowledge that the largest available study regarding CBT for circumferential arthrodesis. Results underlined the safety of this technique and the promising clinical and radiological outcomes that will need a longer follow-up. These slides can be retrieved under Electronic Supplementary material.

Intra-Operative Ultrasound: Tips and Tricks for Making the Most in Neurosurgery.

PURPOSE: Advances in intraoperative imaging and neuronavigation techniques have positively affected glioma surgery. The desire to reduce brain-shift-related problems while achieving the real-time identification of lesions and residual and anatomical relationships has strongly supported the introduction of intraoperative ultrasound (ioUS) in neuro-oncological surgery. This paper presents tips based on our experience with ioUS in neurosurgery. METHODS: We retrospectively analyzed 264 patients who underwent high-grade glioma (HGG) resection at the University of Turin and 60 patients who were treated at the University of Rome. RESULTS: The main issues are the correct choice of the probe and how to evaluate the anatomy to understand how the information from the three common US planes (axial, sagittal and coronal plane) can be used in each case. It is also important to correctly identify anatomical structures in ioUS imaging. In a normal brain, the sulci, sickle, tentorium, choroid plexus, ependyma and the walls of the vessels are all hyperechoic. In addition, some structures are hypoechoic with a homogeneous acoustic gradient: ventricles, cysts and everything that contains liquor. Tumors are usually hyperechoic in ioUS because of their higher cellularity. Conversely, acute edema that contains fluid is hypoechoic, while chronic edema is hyperechoic. CONCLUSIONS: IoUS is a real-time, accurate and inexpensive imaging method. The difficulties of interpretation can be overcome by experience in US imaging and a better understanding of the interaction between navigation and imaging fusion techniques. Training on a large number of cases is important for the correct assessment of ioUS information to obtain valuable, real-time information during HGG surgery.