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.

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.

Complications of degenerative lumbar spondylolisthesis and stenosis surgery in patients over 80 s: comparative study with over 60 s and 70 s. Experience with 678 cases.

PURPOSE: Degenerative spondylolisthesis (DS) is a debilitating condition that carries a high economic burden. As the global population ages, the number of patients over 80 years old demanding spinal fusion is constantly rising. Therefore, neurosurgeons often face the important decision as to whether to perform surgery or not in this age group, commonly perceived at high risk for complications. METHODS: Six hundred seventy-eight elder patients, who underwent posterolateral lumbar fusion for DS (performed in three different centers) from 2012 to 2020, were screened for medical, early and late surgical complications and for the presence of potential preoperative risk factors. Patients were divided in three categories based on their age: (1) 60-69 years, (2) 70-79 years, (3) 80 and over. Multiple logistic regression was used to determine the predictive power of age and of other risk factors (i.e., ASA score; BMI; sex; presence or absence of insulin-dependent and -independent diabetes, use of anticoagulants, use of antiaggregants and osteoporosis) for the development of postoperative complications. RESULTS: In univariate analysis, age was significantly and positively correlated with medical complications. However, when controls for other risk factors were added in the regressions, age never reached significance, with the only noticeable exception of cerebrovascular accidents. ASA score and BMI were the two risk factors that significantly correlated with the higher numbers of complication rates (especially medical). CONCLUSION: Patients of different age but with comparable preoperative risk factors share similar postoperative morbidity rates. When considering octogenarians for lumbar arthrodesis, the importance of biological age overrides that of chronological.

Major complications in extreme lateral interbody fusion access: multicentric study by Italian S.O.L.A.S. group.

PURPOSE: The eXtreme Lateral Interbody Fusion (XLIF) approach has gained increasing importance in the last decade. This multicentric retrospective cohort study aims to assess the incidence of major complications in XLIF procedures performed by experienced surgeons and any relationship between the years of experience in XLIF procedures and the surgeon's rate of severe complications. METHODS: Nine Italian members of the Society of Lateral Access Surgery (SOLAS) have taken part in this study. Each surgeon has declared how many major complications have been observed during his surgical experience and how they were managed. A major complication was defined as an injury that required reoperation, or as a complication, whose sequelae caused functional limitations to the patient after one year postoperatively. Each surgeon was finally asked about his years of experience in spine surgery and XLIF approach. Pearson correlation test was used to evaluate the association between the surgeon's years of experience in XLIF and the rate of major complications; a p-value of last than 0.05 was considered significant. RESULTS: We observed 14 major complications in 1813 XLIF procedures, performed in 1526 patients. The major complications rate was 0.7722%. Ten complications out of fourteen needed a second surgery. Neither cardiac nor respiratory nor renal complications were observed. No significant correlation was found between the surgeon's years of experience in the XLIF procedure and the number of major complications observed. CONCLUSION: XLIF revealed a safe and reliable surgical procedure, with a very low rate of major complications, when performed by an expert spine surgeon.

Superior Osteo-Inductive and Osteo-Conductive Properties of Trabecular Titanium vs. PEEK Scaffolds on Human Mesenchymal Stem Cells: A Proof of Concept for the Use of Fusion Cages.

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative trabecular titanium (T-Ti) scaffold on human mesenchymal stem cells (hMSCs), in both absence and presence of biochemical osteogenic stimuli. Same abilities were assessed on PEEK and standard 2D plastic surface, the latter meant as gold-standard for in vitro differentiation studies. hMSCs adhered and colonized both T-Ti and PEEK scaffolds. In absence of osteogenic factors, T-Ti triggered osteogenic induction of MSCs, as demonstrated by alkaline phosphatase activity and calcium deposition increments, while PEEK and standard 2D did not. Addition of osteogenic stimuli reinforced osteogenic differentiation of hMSCs cultured on T-Ti in a significantly higher manner with respect to standard 2D plastic culture surfaces, whereas PEEK almost completely abolished the process. T-Ti driven differentiation towards osteoblasts was confirmed by gene and marker expression analyses, even in absence of osteogenic stimuli. These results clearly indicate superior in vitro osteo-inductive and osteo-conductive capacity of T-Ti compared to PEEK, and make ground for further studies supporting the use of T-Ti cages to improve bone fusion.

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.

Custom-made trabecular titanium implants for the treatment of lumbar degenerative discopathy via ALIF/XLIF techniques: rationale for use and preliminary results.

PURPOSE: Related to the development and diffusion of ALIF and XLIF, it is possible to correct sagittal malalignment in selected cases of lumbar degenerative discopathy with a relatively low invasiveness. Still, the malposition or the inappropriate size of the implanted cages may lead to the subsidence of the vertebral endplates with loss of correction as well as a decrease in the potential to restore spinal biomechanics in the long run. The aim of this study is to evaluate safety, feasibility, and preliminary clinical and radiological results when using custom-made, trabecular titanium cages in ALIF and XLIF procedures. METHODS: We prospectively evaluated 18 consecutive patients who underwent either an ALIF or an XLIF procedure with the implant of a custom-made, trabecular titanium cage for lumbar degenerative disease with sagittal imbalance, with a minimum of 1-year clinical and radiological follow-up. RESULTS: After a mean follow-up of 14 months, the Oswestry score dropped to a mean of 13 from a preoperative value of 48 (p < 0.0001). Lumbar lordosis was significantly improved, especially in the lower lumbar segment L4-S1 (+ 11 ± 7°; p < 0.0001). No cases of subsidence were noted. CONCLUSIONS: Custom-made, trabecular titanium cages allowed a segmental, steady, durable sagittal correction via ALIF and XLIF approaches. The absence of cage subsidence at 1 year encourages further studies on a larger cohort with longer follow-up. These slides can be retrieved under Electronic Supplementary Material.

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.

Facial Nerve Schwannoma: A Case Report, Radiological Features and Literature Review.

Facial nerve schwannoma localized in the middle fossa is a rare lesion. We report a case of a facial nerve schwannoma in a 30-year-old male presenting with facial nerve palsy. Magnetic resonance imaging (MRI) showed a 3 cm diameter tumor of the right middle fossa. The tumor was removed using a sub-temporal approach. Intraoperative monitoring allowed for identification of the facial nerve, so it was not damaged during the surgical excision. Neurological clinical examination at discharge demonstrated moderate facial nerve improvement (Grade III House-Brackmann).

Cerebrovascular diseases in the elderly: the challenge of multiple aneurysms.

OBJECTIVE: The worldwide population aging and the nowadays medical advances impose to consider new management guidelines for elderly. Aim of this study was to assess the best treatment in elderly with multiple intracranial aneurysms (MIA). METHODS: From 1994 to 2011, we admitted 1462 patients with ruptured cerebral aneurysm. Among those aged ≥65 years, 43 had MIA (15% of elderly). Size and aneurysm location, timing and type of treatment were analyzed. Patients were thus stratified according to Hunt-Hess grade on admission and evaluated at 6 months using the Glasgow Outcome Scale (GOS). RESULTS: We had 87 aneurysms in the final series. Three patients died because of the impossibility to treat the ruptured aneurysm. No new bleeding from untreated aneurysms was observed; no retreatment after previous coiling was performed. CONCLUSIONS: MIA lead to significantly poorer outcomes, especially in elderly, because of their general clinical condition, presence of risk factors and lower capacity of reaction to stressful events. In patients without large hematomas, coiling of the ruptured aneurysm represents the procedure with high effectiveness. The clinical conditions on admission represent the most important factor for the treatment results. To reduce the treatment-related risks we do recommend a conservative approach for the unruptured aneurysms.

A comparison of traditional and net structured intersomatic cages in the lombosacral region: A biomechanical analysis for enhancing discopathy treatment.

The vertebral column represents an essential element for support, mobility, and the protection of the central nervous system. Various pathologies can compromise these vital functions, leading to pain and a decrease in the quality of life. Within the scope of this study, a novel redesign of the Intersomatic Cage, traditionally used in the presence of discopathy, was proposed. The adoption of additive manufacturing technology allowed for the creation of highly complex geometries, focusing on the lumbosacral tract, particularly on the L4-L5 and L5-S1 intervertebral discs. In addition to the tensile analysis carried out using Finite Element Analysis (FEA) in static simulations, a parallel study on the range of motion (ROM) of the aforementioned vertebral pairs was conducted. The ROM represents the relative movement range between various vertebral pairs. The introduction of the intersomatic cage between the vertebrae, replacing the pulpy nucleus of the intervertebral disc, could influence the ROM, thus having significant clinical implications. For the analysis, the ligaments were modelled using a 1D approach. Their constraint reaction and deformability upon load application were analysed to better understand the potential biomechanical implications arising from the adoption of the cages. During the FEA simulations, two types of cages were analysed: LLIF for L4-L5 and ALIF for L5-S1, subjecting them to four different loading conditions. The results indicate that the stresses exhibited by cages with a NET structure are generally lower compared to those of traditional cages. This stress reduction in cages with NET structure suggests a more optimal load distribution, but it is essential to assess potential repercussions on the surrounding bone structure.

Anamnestic radiological metastases outcome surgical score (ARMO-S). A purpose of a predictive surgical scoring system for brain metastases.

BACKGROUND: Several risk stratification scores have been suggested to aid prognostication and guide treatment strategies for brain metastases (BMs). However, the current scores do not focus on the specific neurosurgical population, therefore not predicting short-term mortality and postoperative performance status. METHODS: This retrospective observational study of 362 consecutive patients treated with surgery for BMs aims to identify the factors associated with post-surgical outcomes and propose a surgery-specific prognostic score for patients with BMs candidate for open surgery. RESULTS: Factors significantly associated with OS and performance status in multivariate analysis were age, KPS, surgical site, synchronous debut of BM, number, tumor volume, seizure, extra-cranial metastases, and deep-seated location. The variables were incorporated into the Anamnestic Radiological Metastases Outcome Surgical score (ARMO-S). The values range between 0 and 10. Patients were divided into two groups (low-risk and high-risk) based on each significant subgroup's median survival and performance status with an optimal cutoff value determined as 4. The two groups have significant differences in OS (9.6 versus 14 months, p = 0.0048) postoperative KPS (90 versus 70, p = 0.012) and KPS at last follow-up evaluation (75 versus 30, p < 0.001) CONCLUSION: ARMO-S is a simple and comprehensive score for BM patients selected for neurosurgery, as it incorporates the main factors of the most important prognostic scores, implementing them with more surgery-specific predictive elements such as tumor location and volume, presence of seizures at onset, and involvement of eloquent brain areas.

Single-step resection and reconstruction using patient-specific implants in the treatment of benign cranio-orbital tumors.

PURPOSE: The aim of this study was to evaluate surgical outcomes using patient-specific prostheses produced by computer-aided design and manufacturing for primary reconstruction in patients with benign cranio-orbital tumors. Polyetheretherketone was used to manufacture the implants. MATERIALS AND METHODS: The present study included 3 patients who underwent fronto-orbito-pterional craniotomy using individual custom-made surgical guides. Patient-specific polyetheretherketone prostheses were used for reconstruction during the same surgery. All patients underwent esthetic examination (facial and orbital symmetry, globe projection and position), ophthalmologic examination (diplopia with the Hess-Lancaster test, visual field and acuity), and radiologic evaluations (computed tomography and magnetic resonance imaging) during the preoperative and follow-up periods. Operating time and short- and long-term complications were recorded. RESULTS: The immediate and long-term morphologic results were satisfactory; in particular, ocular globe position and projection were correct. After 25 to 31 months, none of the patients developed implant-related complications, such as infection, extrusion, or malposition. Two-year postoperative computed tomograms and magnetic resonance images showed no recurrences. CONCLUSION: Single-step resection and reconstruction with computer-aided designed and manufactured implants is a challenging new technique that decreases operative time and morbidity. The implants adequately restore an anatomically complex area with satisfactory cosmetic results.

A retrospective two-center study of antiepileptic prophylaxis in patients with surgically treated high-grade gliomas.

BACKGROUND: The effectiveness of antiepileptic prophylaxis in patients with newly diagnosed high-grade glioma is debated. Craniotomy, surgical manipulation and bleeding are believed to favor the onset of seizures and, therefore, perioperative antiepileptic drugs (AEDs) are generally used. Nevertheless, evidence to initiate preoperative AED prophylaxis are weak. AIM: Aim of this paper was to evaluate the need for AED prophylaxis in surgically-treated malignant glioma patients without history of seizures. MATERIALS AND METHODS: We conducted a retrospective, two-center cohort study to assess the effectiveness of preoperative AED prophylaxis. Patients were divided in two groups: one with AED preoperative administration and the other without. Because of its non-hepatic metabolism, levetiracetam (LEV) was chosen. Logistic regression models were used to investigate the odds ratio for each group. The explanatory variables included the treatment received, sex, age, and site of lesion. The outcome measure of successful LEV prophylaxis was seizure vs. no seizure post-operatively, at three and six months after surgery. RESULTS: Our results showed that LEV prophylaxis was not a significant predictor of seizure occurrence, although the regression coefficient indicated a slight reduction in seizure risk following LEV administration. Patient's age was a significant predictor of seizure occurrence. Younger patients had a higher risk of seizure in the six months post-surgery. CONCLUSIONS: We conclude that AEDs prophylaxis does not provide a substantial benefit to surgically treated high-grade glioma patients and should not be administered routinely. Further investigations are required to detect subgroups of patients at higher risk of developing seizures in order to selectively administer AED.

How Reliable Is Fluorescence-Guided Surgery in Low-Grade Gliomas? A Systematic Review Concerning Different Fluorophores.

BACKGROUND: Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas. METHODS: A systematic review was conducted. 5-aminolevulinic acid, sodium fluorescein, indocyanine green and tozuleristide were taken into account. The main considered outcome was the fluorescence rate, defined as the number of patients in whom positive fluorescence was detected out of the total number of patients. Only low-grade gliomas were considered, and data were grouped according to single fluorophores. RESULTS: 16 papers about 5-aminolevulinic acid, 4 about sodium fluorescein, 2 about indocyanine green and 1 about tozuleristide were included in the systematic review. Regarding 5-aminolevulinic acid, a total of 467 low-grade glioma patients were included, and fluorescence positivity was detected in 34 out of 451 Grade II tumors (7.3%); while in Grade I tumors, fluorescence positivity was detected in 9 out of 16 cases. In 16 sodium fluorescein patients, seven positive fluorescent cases were detected. As far as indocyanine is concerned, two studies accounting for six patients (three positive) were included, while for tozuleristide, a single clinical trial with eight patients (two positive) was retrieved. CONCLUSIONS: The current evidence does not support the routine use of 5-aminolevulinic acid or sodium fluorescein with a standard operating microscope because of the low fluorescence rates. New molecules, including tozuleristide, and new techniques for fluorescence detection have shown promising results; however, their use still needs to be clinically validated on a large scale.

Can Post-Operative Posterior Reversible Encephalopathy Syndrome (PRES) Be Considered an Insidious Rare Surgical Complication?

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by neurological symptoms and distinctive neuroimaging findings. There are a few cases reported in the literature in which PRES can occur after surgery, and there is no clear direct relationship between a procedure and its debut. Methods: We performed a review of the literature by analyzing all reported cases of PRES syndrome which debuted after a surgical procedure with the aim of identifying the clinical features, the timing of the symptoms' onset and the therapy of patients suffering from this unusual surgical complication. Results: The total number of patients collected was 47, with a mean age of 40.9 years. Postoperative PRES can occur in either pediatric or adult patients (ages 4-82 years). The most frequent form of comorbidity reported was cardiovascular disease (fourteen patients, 29.78%). Sixteen patients (36%) had no relevant risk factors or comorbidities at the time of the surgical procedure. The types of surgery most correlated were cranial neuro and maxillofacial surgery (twenty-one patients, 44.68%) followed by transplant surgery (eight patients, 17%). The time of onset of PRES after surgery occurred within the first 3 weeks (mean time of onset 4.7 days), and when rapidly treated with antihypertensive and antiepileptic drugs appeared to have a reversible and benign course. Conclusion: PRES syndrome can be considered a rare complication of procedures and can occur following a wide range of surgeries, especially cranial and transplant surgery. Being able to recognize it in time and treat it ensures a full reversibility of symptoms in most cases.