How I do it: flexible endoscopic aspiration of intraventricular hemorrhage

Background: As intraventricular blood is a strong negative prognostic factor, intraventricular hemorrhage requires prompt and aggressive management to reduce intracranial hypertension. Method: A flexible scope can be used to navigate and to aspirate blood clots from all four ventricles. Complete restoration of CSF pathways from the lateral ventricle to the foramen of Magendie can be obtained. Conclusion: Flexible neuroendoscopic aspiration of IVH offers the opportunity to immediately reduce intracranial hypertension, reduce EVD obstruction and replacement rates, and decrease infections and shunt dependency

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

Background: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results: Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral (n = 8, 44.4%), followed by clivus (n = 7, 38.9%) and lumbar spine (n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery (n = 10, 55.6%), RT (n = 9, 50.0%), and systemic treatments (n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions: This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes

Current status and future perspectives on stem cell transplantation for spinal cord injury

Background: Previous assessments of stem cell therapy for spinal cord injuries (SCI) have encountered challenges and constraints. Current research primarily emphasizes safety in early-phase clinical trials, while systematic reviews prioritize effectiveness, often overlooking safety and translational feasibility. This situation prompts inquiries regarding the readiness for clinical adoption. Aim: To offer an up-to-date systematic literature review of clinical trial results con cerning stem cell therapy for SCI. Methods: A systematic search was conducted across major medical databases [PubMed, Embase, Reference Citation Analysis (RCA), and Cochrane Library] up to October 14, 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "spinal cord", "injury", "clinical trials", "stem cells", "functional outcomes", and "adverse events". Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI. Results: In a comprehensive review of 66 studies on stem cell therapies for SCI, 496 papers were initially identified, with 237 chosen for full-text analysis. Among them, 236 were deemed eligible after excluding 170 for various reasons. These studies encompassed 1086 patients with varying SCI levels, with cervical injuries being the most common (42.2%). Bone marrow stem cells were the predominant stem cell type used (71.1%), with various administration methods. Follow-up durations averaged around 84.4 months. The 32.7% of patients showed functional impro vement from American spinal injury association Impairment Scale (AIS) A to B, 40.8% from AIS A to C, 5.3% from AIS A to D, and 2.1% from AIS B to C. Sensory improvements were observed in 30.9% of patients. A relatively small number of adverse events were recorded, including fever (15.1%), headaches (4.3%), muscle tension (3.1%), and dizziness (2.6%), highlighting the potential for SCI recovery with stem cell therapy. Conclusion: In the realm of SCI treatment, stem cell-based therapies show promise, but clinical trials reveal potential adverse events and limitations, underscoring the need for meticulous optimization of transplantation conditions and parameters, caution against swift clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before gradual and careful adoption in clinical practice

Endoscopic evacuation of massive intraventricular hemorrhages reduces shunt dependency: a meta-analysis

Intraventricular hemorrhage (IVH) is characterized by severe prognosis. The amount of intraventricular blood is the most important, disease-specific, prognostic factor, as acute complications are strictly dependent on clot formation. Although external ventricular drain (EVD) placement is the standard treatment, in the past 15 years neuroendoscopic (NE) evacuation of IVH has been advocated, but available comparative data are limited. A systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included articles compare the treatment of primary and secondary IVH with NE and EVD. The meta-analysis was performed in terms of shunt dependency. Cochran's Q-test and I2 statistics were used to assess heterogeneity in the studies. No heterogeneity was considered for p greater than 0.05 and I2 less than 20%. A random-effect model was used, with restricted maximum likelihood to estimate the heterogeneity variance. After screening 744 articles, 5 were included in the meta-analysis. A total of 303 patients presenting with primary or pure (50 patients) and secondary (253 patients) IVH, undergoing either NE (151) or EVD (152), were included in the metanalysis. The risk of ventriculoperitoneal (VP) shunt was higher in the EVD group (relative risk: 1.93, 95% confidence interval: 1.28-2.92, p  = 0.0094). The risk of VP shunt was higher in the EVD group, but the overall outcome remains poor for patients with IVH, with a moderate-to-high disability. Large randomized controlled trials are needed to evaluate more deeper both advantages and effects on the outcome of NE over EVD

Endoscopic anatomy of the fourth ventricle

Object Microsurgical anatomy of the fourth ventricle has been comprehensively addressed by masterly reports providing classic descriptions of this complex region. Neuroendoscopy could offer a new, somewhat different perspective of the "inside" view of the fourth ventricle. The purpose of this study was to examine from the anatomical point of view the access to the fourth ventricle achieved by the endoscopic transaqueductal approach, to enumerate and describe the anatomically identifiable landmarks, and to compare them with those described during microsurgery. Methods The video recordings of 52 of 75 endoscopic explorations of the fourth ventricle performed at the authors' institution for different pathological conditions were reviewed and evaluated to identify and describe every anatomical landmark. According to the microsurgical anatomy, at least 23 superficial structures are clearly identifiable in the fourth ventricle, and they represent the comparative basis of parallel endoscopic anatomy of the structures found during the fourth ventricle navigation. Results The following anatomical structures were identified in all cases: median sulcus, superior and inferior vela medullare, choroid plexus, inferior fovea, hypoglossal and vagal triangles, area postrema, obex, canalis medullaris, lateral recess, and the foramina of Luschka and Magendie. The median eminence, facial colliculus, striae medullaris, auditory tubercle, and inferior fovea were seen in the majority of cases. The locus caevruleus could never be seen. Conclusions On the whole, 20 anatomical structures could consistently be identified by exploring the fourth ventricle with a fiberscope. Neuroendoscopy offers a quite different outlook on the anatomy of the fourth ventricle, and compared with the microsurgical descriptions it seems to provide a superior and detailed visualization, particularly of the structures located in the inferior triangle

Epidemiology-based evaluation of trends in treatment for ruptured intracranial aneurysms in Italy

Background: In recent years there have been significant advances in the diagnosis, management and treatment of intracranial aneurysms (IAs) in Italy. Changes in prevalence of several epigenetic risk factors in the population as well as in environmental factors may have influenced the epidemiological burden of this disease. No long-term, population-based study about the incidence of treated ruptured IAs (rIAs) in Italy has yet been reported in literature. Methods: A long-term (January 2015 - December 2020), nationwide epidemiology study was performed by using discharge data collected by the Italian National Agency for Regional Healthcare Services with a particular focus on the treatment incidence of rIAs. A sub-analysis per macro-areas (north, center, and south and islands) was also performed, including the data about regional healthcare systems organization. The prevalence of common epigenetic and environmental risk factors has been also assessed. Results: Over 6 years, the mean incidence of rIAs treatment was 2.7 x 100.000 per year (ds ± 0.1; range: 2.6-2.9). In 2020, there was a significant north-south decreasing gradient in incidence (north vs center vs south and islands: 3.4 vs 2.4 vs 1.8 x 100.000/year; all p<0.001). There were no meaningful differences between macro-areas in terms of access to emergency care and number of neurosurgical wards per population. The rate of unruptured IAs (uIAs) treatment did not show a correlation to that of ruptured ones. Minor regional differences were retrieved for high-risk hypertension as well as for alcohol abuse prevalence. Air pollutants and temperature charts showed a north-south gradient similar to that of the incidence in the treated rIAs. Conclusions: The mean incidence of treated rIAs was stable over the 2015-2020 period in Italy. A north-south decreasing gradient in rIAs treatment incidence was reported. Neither the Regional healthcare organizations nor the rate of uIAs treatment were significant factors explaining the regional differences in the incidence of rIAs treatment. Minor differences in epigenetic and environmental risk factors may be synergistically involved

Advancing Craniopharyngioma Management: A Systematic Review of Current Targeted Therapies and Future Perspectives

Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients

Efficacy and safety of flexible versus rigid endoscopic third ventriculostomy in pediatric and adult populations: a systematic review and meta-analysis

Endoscopic third ventriculostomy (ETV) is a well-established surgical procedure for hydrocephalus treatment, but there is sparse evidence on the optimal choice between flexible and rigid approaches. A meta-analysis was conducted to compare efficacy and safety profiles of both techniques in pediatrics and adults. A comprehensive search was conducted on PubMED, EMBASE, and Cochrane until 11/10/2019. Efficacy was evaluated comparing incidence of ETV failure, while safety was defined by the incidence of perioperative complications, intraoperative bleedings, and deaths. Random-effects models were used to pool the incidence. Out of 1365 studies, 46 case series were meta-analyzed, yielding 821 patients who underwent flexible ETV and 2918 who underwent rigid ETV, with an age range of [5&nbsp;days-87&nbsp;years]. Although flexible ETV had a higher incidence of failure in adults (flexible: 54%, 95%CI: 22-82% vs rigid: 20%, 95%CI: 22-82%) possibly due to confounding due to etiology in adults treated with flexible, a smaller difference was seen in pediatrics (flexible: 36%, pediatric: 32%). Safety profiles were acceptable for both techniques, with a certain degree of variability for complications (flexible 2%, rigid 18%) and death (flexible 1%, rigid 3%) in pediatrics as well as complications (rigid 9%, flexible 13%), death (flexible 4%, rigid 6%) and intra-operative bleeding events (rigid 6%, flexible 8%) in adults. No clear superiority in efficacy could be depicted between flexible and rigid ETV for hydrocephalus treatment. Safety profiles varied by age but were acceptable for both techniques. Well-designed comparative studies are needed to assess the optimal endoscopic treatment option for hydrocephalus

Hemorrhagic stroke: endoscopic aspiration

Intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) carry a very dismal prognosis. Several medical and surgical attempts have been made to reduce mortality and to improve neurological outcomes in survivors. Aggressive surgical treatment of ICH through craniotomy and microsurgical evacuation did not prove to be beneficial to these patients, compared to the best medical treatment. Similarly, the conventional treatment of IVH using an EVD is often effective in controlling ICP only initially, as it is very likely for the EVD to become obstructed by blood clots, requiring frequent replacements with a consequent increase of infection rates.Minimally invasive techniques have been proposed to manage these cases. Some are based on fibrinolytic agents that are infused in the hemorrhagic site through catheters with a single burr hole. Others are possible thanks to the development of neuroendoscopy. Endoscopic removal of ICH through a mini-craniotomy or a single burr hole, and via a parafascicular white matter trajectory, proved to reduce mortality in this population, and further randomized trials are expected to show whether also a better neurological outcome can be obtained in survivors. Moreover, endoscopy offers the opportunity to access the ventricular system to aspirate blood clots in patients with IVH. In such cases, the restoration of patency of the entire CSF pathway has the potential to improve outcome and reduce complications and now it is believed to decrease shunt-dependency

The subependymal microvascular network revealed by endoscopic fluorescence angiography

BACKGROUND: The subependymal vascularization of the cerebral ventricles has been described in anatomical studies on human specimens. Its identification in vivo during neuroendoscopic navigation could have anatomical interest and may lead to a safer ventricular navigation, also avoiding unexpected bleeding. The traditional endoscopic visualization allows the certain identification of only the main vessels. In this study we describe the features of the subependymal vascular network (SEVN) enhanced by sodium fluorescein (SF) angiography. We compare these findings with the vascular patterns visible under white light to evaluate the sensitivity of this technique in unveiling the most distant branches of the SEVN.METHODS: We reviewed the video records of 39 fluorescein-assisted neuroendoscopic procedures. Steerable fiberscopes equipped with a dual observation mode for both white light and fluorescence were used. After preliminary inspection of the ventricular cavities, the camera was switched to the blue light fluorescent mode. Identical portion of ventricular walls observed in both modalities were compared and analyzed to enhance potential differences of the vascular features.RESULTS: The main veins were positive (fluorescein enhanced) in 10 patients (25.6%), vessels of smaller diameter visible also under white light presented a detectable fluorescence in 27 patients (69.2%), the micro SEVN, not visible under with light, was revealed by SF in 21 patients (53.8%).CONCLUSIONS: Fluorescein-guided neuroendoscopy deserves closer investigation since it allows detection of small vessels, not otherwise visible, in the ventricle walls. This method could be applied to ameliorate the knowledge of the environment the surgeon is working on. leading as a result to a safer navigation, also by avoiding minor bleedings