Lesson learned in endoscopic endonasal dens resection for C1-C2 spinal cord decompression.

PURPOSE: Endoscopic endonasal approach (EEA) is the safest and most effective technique for odontoidectomy. Nevertheless, this kind of approach is yet not largely widespread. The aim of this study is to share with the scientific community some tips and tricks with our ten-year-old learned experience in endoscopic endonasal odontoidectomy (EEO), which remains a challenging surgical approach. MATERIAL AND METHODS: Our case series consists of twenty-one (10 males, 11 females; age range of 34-84 years) retrospectively analyzed patients with ventral spinal cord compression for non-reducible CVJ malformation, treated with EEA from July 2011 to March 2019. RESULTS: The results have recently been reported in a previous paper. The only intraoperative complication observed was intraoperative cerebrospinal fluid (CSF) leak (9.5%), without any sign of post-operative CSF leak. CONCLUSIONS: Considering our experience, EEO represents a valid and safe technique to decompress neural cervical structures. Despite its technical complexity, mainly due to the use of endoscope and the challenging surgical area, with this study we encourage the use of EEO displaying our experience-based surgical tips and tricks.

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.

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

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.

To use or not to use antithrombotics in unruptured cerebrovascular malformations? A systematic review focusing on this clinical and surgical dilemma.

OBJECTIVE: Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease. METHODS: The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear. CONCLUSIONS: The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.

Early versus delayed mobilization after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of efficacy and safety.

OBJECTIVE: A central tenet of Enhanced Recovery After Surgery (ERAS) is evidence-based medicine. Survivors of aneurysmal subarachnoid hemorrhage (aSAH) constitute a fragile patient population prone to prolonged hospitalization within neurointensive care units (NICUs), prolonged immobilization, and a range of nosocomial adverse events. Potentially, well-monitored early mobilization (EM) could constitute a beneficial element of ERAS protocols in this population. Therefore, the objective was to summarize the available evidence on EM strategies in patients with aSAH. METHODS: The authors retrieved prospective and retrospective studies that reported efficacy or safety data on EM (defined as EM in the NICU starting ≤ 7 days after ictus) versus delayed mobilization (DM) (any strategy that comparatively delayed mobilization) after aSAH and were published after January 1, 2000, in PubMed/MEDLINE, Embase, and the Cochrane Library. Random-effects meta-analysis was performed. RESULTS: Ten studies analyzing 1292 patients were included for quantitative synthesis, including 1 randomized, 1 prospective nonrandomized, and 8 retrospective studies. Modified Rankin Scale scores at discharge were not different between the EM and DM groups (mean difference [MD] [95% CI] -0.86 [-2.93 to 1.20] points, p = 0.41). Hospital length of stay in days was markedly reduced in the EM group (MD [95% CI] -6.56 [-10.64 to -2.47] days, p = 0.002). Although there was a statistically significant reduction in radiological vasospasms (OR [95% CI] 0.65 [0.44-0.97], p = 0.03), the reduction in clinically relevant vasospasms was nonsignificant (OR [95% CI] 0.63 [0.31-1.26], p = 0.19). The odds of shunting were significantly lower in the EM group (OR [95% CI] 0.61 [0.39-0.95], p = 0.03). The rates of mortality, pneumonia, and thrombosis were similar among groups (p > 0.05). CONCLUSIONS: Due to a lack of high-quality studies, vastly varying protocols, and resulting statistical clinical and statistical heterogeneity, the level of evidence for recommendations regarding EM in patients with aSAH remains low. The currently available data indicated that mobilization within the first 5 days after aneurysm repair was feasible and safe without significant excessive adverse events, that neurological outcome with EM was almost certainly not worse than with prolonged immobilization, and that there was likely at least some reduction in length of hospital stay. Radiological and clinical vasospasms were not more frequent-with signals even trending toward a decrease-in patients who mobilized early. Higher-quality studies and implementation of full ERAS protocols are necessary to evaluate efficacy and safety with a higher level of evidence and to guide practical implementation through increased standardization. Clinical trial registration no.: CRD42023432828 (www.crd.york.ac.uk/prospero).

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.

Traumatic peripheral nerve injuries: a classification proposal.

BACKGROUND: Peripheral nerve injuries (PNIs) include several conditions in which one or more peripheral nerves are damaged. Trauma is one of the most common causes of PNIs and young people are particularly affected. They have a significant impact on patients' quality of life and on the healthcare system, while timing and type of surgical treatment are of the utmost importance to guarantee the most favorable functional recovery. To date, several different classifications of PNIs have been proposed, most of them focusing on just one or few aspects of these complex conditions, such as type of injury, anatomic situation, or prognostic factors. Current classifications do not enable us to have a complete view of this pathology, which includes diagnosis, treatment choice, and possible outcomes. This fragmentation sometimes leads to an ambiguous definition of PNIs and the impossibility of exchanging crucial information between different physicians and healthcare structures, which can create confusion in the choice of therapeutic strategies and timing of surgery. MATERIALS: The authors retrospectively analyzed a group of 24 patients treated in their center and applied a new classification for PNI injuries. They chose (a) five injury-related factors, namely nerve involved, lesion site, nerve type (whether motor, sensory or mixed), surrounding tissues (whether soft tissues were involved or not), and lesion type-whether partial/in continuity or complete. An alphanumeric code was applied to each of these classes, and (b) four prognostic codes, related to age, timing, techniques, and comorbidities. RESULTS: An alphanumeric code was produced, similar to that used in the AO classification of fractures. CONCLUSIONS: The authors propose this novel classification for PNIs, with the main advantage to allow physicians to easily understand the characteristics of nerve lesions, severity, possibility of spontaneous recovery, onset of early complications, need for surgical treatment, and the best surgical approach. LEVEL OF EVIDENCE: according to the Oxford 2011 level of evidence, level 2.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

Endoscopic endonasal odontoidectomy: a long-term follow-up results for a cohort of 21 patients.

BACKGROUND: Endoscopic endonasal odontoidectomy (EEO) has been described as a potential approach for craniovertebral junction (CVJ) disease which could cause anterior bulbomedullary compression and encroaching. Due to the atlantoaxial junction's uniqueness and complex biomechanics, treating CVJ pathologies uncovers the challenge of preventing C1-C2 instability. A large series of patients treated with endonasal odontoidectomy is reported, analyzing the feasibility and necessity of whether or not to perform posterior stabilization. Furthermore, the focus is on the long-term follow-up, especially those whom only underwent partial C1 arch preservation without posterior fixation. METHODS: This study is a retrospective analysis of patients with ventral spinal cord compression for non-reducible CVJ malformation, consecutively treated with EEO from July 2011 to March 2019. Postoperative dynamic X-ray and CT scans were obtained in each case in order to document CVJ decompression as well as to exclude instability. The anterior atlas-dens interval, posterior atlas-dens interval and C1-C2 total lateral overhang were measured as a morphological criteria to determine upper cervical spine stability. RESULTS: Twenty-one patients (11:10 F:M) with a mean age of 60.6 years old at the time of surgery (range 34-84 years) encountered the inclusion criteria. For all 21 patients, a successful decompression was achieved at the first surgery. In 11 patients, the partial C1 arch integrity did not require a posterior cervical instrumentation on the bases of postoperative and constant follow-up radiological examination. In 13 cases, an improvement of motor function was recorded at the time of discharge. Only one patient had further motor function improvement at follow-up. Among the patients that did not show any significant motor change at discharge, 4 patients showed an improvement at the last follow-up. CONCLUSIONS: The outcomes, even in C1 arch preservation without posterior fixation, are promising, and it could be said that the endonasal route potentially represents a valid option to treat lesions above the nasopalatine line.

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.

Distant Recurrence of a Cerebral Cavernous Malformation in the Vicinity of a Developmental Venous Anomaly: Case Report of Local Oxy-Inflammatory Events.

BACKGROUND: Cerebral cavernous malformations (CCMs) are a major type of cerebrovascular lesions of proven genetic origin that occur in either sporadic (sCCM) or familial (fCCM) forms, the latter being inherited as an autosomal dominant condition linked to loss-of-function mutations in three known CCM genes. In contrast to fCCMs, sCCMs are rarely linked to mutations in CCM genes and are instead commonly and peculiarly associated with developmental venous anomalies (DVAs), suggesting distinct origins and common pathogenic mechanisms. CASE REPORT: A hemorrhagic sCCM in the right frontal lobe of the brain was surgically excised from a symptomatic 3 year old patient, preserving intact and pervious the associated DVA. MRI follow-up examination performed periodically up to 15 years after neurosurgery intervention demonstrated complete removal of the CCM lesion and no residual or relapse signs. However, 18 years after surgery, the patient experienced acute episodes of paresthesia due to a distant recurrence of a new hemorrhagic CCM lesion located within the same area as the previous one. A new surgical intervention was, therefore, necessary, which was again limited to the CCM without affecting the pre-existing DVA. Subsequent follow-up examination by contrast-enhanced MRI evidenced a persistent pattern of signal-intensity abnormalities in the bed of the DVA, including hyperintense gliotic areas, suggesting chronic inflammatory conditions. CONCLUSIONS: This case report highlights the possibility of long-term distant recurrence of hemorrhagic sCCMs associated with a DVA, suggesting that such recurrence is secondary to focal sterile inflammatory conditions generated by the DVA.

Focal seizures with impaired awareness as long-term neurological complication of COVID-19: a case report.

We report here the first case of a young individual otherwise healthy, who presented with frequent focal seizures with impaired awareness as a possible long-term complication of severe acute respiratory syndrome coronavirus-2 infection. Seizures were documented by electroencephalography and responded clinically and neuro-physiologically to antiseizure therapy. The patient underwent an extensive investigation including cerebrospinal fluid examination, conventional and quantitative brain magnetic resonance imaging, and 18-FDG positron emission tomography. Beyond the clinical interest, this case contributes to clarify the possible pathways by which SARS-CoV-2 may enter the central nervous system and cause long-term neurological complications.

Lenz microphthalmia syndrome in neurosurgical practice: a case report and review of the literature.

Lenz microphthalmia syndrome (LMS) is an allelic X-linked syndrome correlated to a null mutation of B cell lymphoma (BCL-6) corepressor (BCOR) gene, which is essential in the early embryonic development. Phenotypically, this rare hereditary syndrome is characterized by microphthalmia/anophthalmia and other eye disorders; mental disability; dental, ear, and digital abnormalities; and variable malformations affecting the heart, skeleton (limbs and/or spine), and genitourinary tract. In this paper, a case of a young adult with LMS affected additionally by immuno-hematological disturbances was treated with decompressive craniectomy after domestic accidental fall. Case description and a brief review of the current literature about this rare condition are presented here.

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.

Double cystic brain metastasis in a patient with stable pancreatic intraductal papillary mucinous neoplasm.

BACKGROUND: Brain metastases in pancreatic cancer are a rare condition and are usually seen in case of pancreatic adenocarcinoma. Only few cases of brain metastasis in patients affected by Intraductal papillary mucinous neoplasm (IPMN) are actually reported. CASE DESCRIPTION: We report a patient diagnosed with double cystic brain lesions that the histological examination reveal to be consistent, with pancreatic metastasis. Our patient had an history shown of stable pancreatic IPMN which has never made the oncologist suspicious about neoplastic progression or degeneration into pancreatic carcinoma. Considering the rarity of these metastasis we did a literature review on the topic. CONCLUSIONS: Despite rare, pancreatic origin of a cystic brain metastasis should considered in differential diagnosis in both patient with IPMN or patient with unknown primitive tumor.

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.

Neuroform Atlas stent-assisted coiling of ruptured intracranial aneurysms: A multicenter study.

PURPOSE: To assess efficacy, safety and to discuss optimal medical therapy of stent-assisted coiling of ruptured intracranial aneurysms. METHODS: Ruptured intracranial aneurysms treated with stent-assisted coiling in eight different institutions were retrospectively reviewed. Medical treatment regimens varied among the centers, mainly regarding heparin administration and post-procedural single or double antiplatelet therapy. Clinical and angiographic results, including complications and outcomes were analyzed and related to the different therapies. RESULTS: Sixty-one consecutive patients (male/female 23/38), aged 59.1 years (36-86) underwent stent-assisted coiling for ruptured intracranial aneurysm without antiplatelet pre-medication. Intravenous acetylsalicylic acid (ASA) 500mg was administered to all patients immediately after stent deployment. At the same time heparin was given as bolus in 15 patients (24.6%) as part of local protocol. Intravenous glycoprotein 2b/3a inhibitors (antiGP2b3a) were used as bail-out therapy for stent thrombosis. Stent thrombosis occurred in 22 patients (36.1%), of which 4 (6.5%) lead to incomplete and 18 (29.6) to complete occlusion of the stent. Heparin administration had no effect on thrombosis rate. Thrombosis resolution occurred in all cases with intravenous antiGP2b3a (7 tirofiban, 15 abciximab), without increasing overall complication rate. Single antiplatelet therapy with ASA (28 patients, 45.9%) or double antiplatelet therapy including ASA and clopidogrel (33 patients, 54.1%) were administered after procedure, depending on local protocols and on neurointerventionists' experience. Overall complication rate, including ischemia and hemorrhage was higher in patients in which only ASA was administered (21.4% vs. 12.1%). No late stent thrombosis was seen, regardless of whether a single or double antiplatelet regimen was used. Nevertheless, the small sample size suggests caution in interpreting these results. Moreover, a possible bias may arise from the decision whether to modify the maintenance therapy or not depending on the severity of the intracranial hemorrhage in a case-by-case assessment. At three months, 34 out of 38 patients with HH grade 1-2 (89.4%), and 11 out of 23 with Hunt-Hess grade of 3-4 (47.8%) were independent (Modified Ranking Scale 0-2). CONCLUSION: Stent assisted coiling of ruptured intracranial aneurysms is a feasible option when simple coiling is not possible. Optimal medical treatment is still controversial because balance between hemorrhagic and ischemic risks is difficult to evaluate. In our series, heparin bolus had no effect on subsequent stent thrombosis. In all cases peri-operative stent thrombosis was successfully managed using bail-out intravenous antiGP2b3a, which did not increase post-procedural hemorrhage rates. A non-significant trend towards increased complications rate was noticed in patients treated with single antiplatelet therapy versus double antiplatelet therapy.