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.

Hinge craniotomy versus standard decompressive hemicraniectomy: an experimental preclinical comparative study.

INTRODUCTION: Decompressive craniectomy (DC) is the most common surgical procedure to manage increased intracranial pressure (ICP). Hinge craniotomy (HC), which consists of fixing the bone operculum with a pivot, is an alternative method conceived to avoid some DC-related complications; nonetheless, it is debated whether it can provide enough volume expansion. In this study, we aimed to analyze the volume and ICP obtained with HC using an experimental cadaver-based preclinical model and compare the results to baseline and DC. METHODS: Baseline conditions, HC, and DC were compared on both sides of five anatomical specimens. Volume and ICP values were measured with a custom-made system. Local polynomial regression was used to investigate volume differences. RESULTS: The area of the bone opercula resulting from measurements was 115.55 cm2; the mean supratentorial volume was 955 mL. HC led to intermediate results compared to baseline and DC. At an ICP of 50 mmHg, HC offers 130 mL extra space but 172 mL less than a DC. Based on local polynomial regression, the mean volume difference between HC and the standard craniotomy was 10%; 14% between DC and HC; both are higher than the volume of brain herniation reported in the literature in the clinical setting. The volume leading to an ICP of 50 mmHg at baseline was less than the volume needed to reach an ICP of 20 mmHg after HC (10.05% and 14.95% from baseline, respectively). CONCLUSIONS: These data confirm the efficacy of HC in providing sufficient volume expansion. HC is a valid intermediate alternative in case of potentially evolutionary lesions and non-massive edema, especially in developing countries.

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.

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 days-87 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.

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

Anxiety in neurosurgical patients undergoing nonurgent surgery during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has forced many countries into lockdown and has led to the postponement of nonurgent neurosurgical procedures. Although stress has been investigated during this pandemic, there are no reports on anxiety in neurosurgical patients undergoing nonurgent surgical procedures. METHODS: Neurosurgical patients admitted to hospitals in eastern Lombardy for nonurgent surgery after the lockdown prospectively completed a pre- and postoperative structured questionnaire. Recorded data included demographics, pathology, time on surgical waiting list, anxiety related to COVID-19, primary pathology and surgery, safety perception during hospital admission before and after surgery, and surgical outcomes. Anxiety was measured with the State-Trait Anxiety Inventory. Descriptive statistics were computed on the different variables and data were stratified according to pathology (oncological vs nononcological). Three different models were used to investigate which variables had the greatest impact on anxiety, oncological patients, and safety perception, respectively. Because the variables (Xs) were of a different nature (qualitative and quantitative), mostly asymmetrical, and related to outcome (Y) by nonlinear relationships, a machine learning approach composed of three steps (1, random forest growing; 2, relative variable importance measure; and 3, partial dependence plots) was chosen. RESULTS: One hundred twenty-three patients from 10 different hospitals were included in the study. None of the patients developed COVID-19 after surgery. State and trait anxiety were reported by 30.3% and 18.9% of patients, respectively. Higher values of state anxiety were documented in oncological compared to nononcological patients (46.7% vs 25%; p = 0.055). Anxiety was strongly associated with worry about primary pathology, surgery, disease worsening, and with stress during waiting time, as expected. Worry about positivity to SARS-CoV-2, however, was the strongest factor associated with anxiety, even though none of the patients were infected. Neuro-oncological disease was associated with state anxiety and with worry about surgery and COVID-19. Increased bed distance and availability of hand sanitizer were associated with a feeling of safety. CONCLUSIONS: These data underline the importance of psychological support, especially for neuro-oncological patients, during a pandemic.

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.

New perspectives in the endoscopic treatment of brain purulent collections: targets, techniques, results in a case series, and overview of the literature.

BACKGROUND: Purulent intracranial infections are threatening conditions. Different surgical approaches have been described, respecting the rationale of evacuating the fluid component of the purulent collection. Emerging evidence supports the use of the endoscope for the treatment of cerebral abscesses and subdural empyemas; especially the peculiarities of flexible endoscopes could potentially offer a more effective and conclusive management as compared with the drainage through catheters. We describe our experience in the treatment of intracranial purulent collections with flexible endoscopy, comparing it with the most recent literature. METHODS: Ten patients affected by intracranial suppuration were treated with endoscopy at our institution. The neurosurgical technique is thoroughly described. The related literature is reviewed, providing a comprehensive overview on the endoscopic treatment of intracranial suppuration so far. RESULTS: All the patients had a good clinical outcome, with no peri-operative complications. The postoperative scans showed significant radiological improvement, with important reduction of the pus volume. In all cases, the microbiological cultures showed positivity. CONCLUSIONS: In our experience, the use of the flexible scope proved feasible and effective in the treatment of intracranial purulent collections. Visual awareness of the internal capsule is not limited to a direct inspection of the fluid pus; it rather allows an active removal of the more solid (and perhaps more microbiologically significant) fibrinoid component, and also assists in final bleeding control and in assessing the extent of the evacuation. The steering capabilities of the fiberscope are particularly suitable for such purposes, allowing sampling the solid internal layer of the pyogenic membrane, and potentially shedding light on the actual clinical significance of this component of the abscess.

Split cerebral aqueduct: a neuroendoscopic illustration.

PURPOSE: Forking of the cerebral aqueduct is a developmental malformation that is infrequently encountered by neurosurgeons as a rare cause of hydrocephalus, sometimes with a delayed onset. The etiology of an apparently forked aqueduct might be different. However, neuroendoscopy can often be the optimal treatment. The purpose of this study was to review the literature by analyzing the anatomical, functional, diagnostic, and therapeutic features of this unusual condition and adding our personal cases. METHODS: We present a case of forking of the cerebral aqueduct that was detected in vivo and treated with a flexible scope. A thorough review of the pertinent literature is also discussed. In the past years, diagnosis of forked aqueduct was possible only postmortem. RESULTS: A forked aqueduct is occasionally encountered in patients when a delayed hydrocephalic decompensation occurs. CONCLUSIONS: Flexible neuroendoscopy enables for a direct, in vivo diagnosis and immediate treatment through a third ventriculostomy.

Aspiration of parafalcine empyemas with flexible scope.

PURPOSE: Subdural empyemas are considered neurosurgical emergencies, and the parafalcine location is particularly insidious. We revised the experience of general surgeons who are used to manage chronic pleural purulent collections with video-assisted thoracoscopy. METHODS: With a similar technique, we successfully aspirated a parafalcine empyema using a flexible scope avoiding a more invasive craniotomy. A review of the treatment options of empyematous collections is also provided, focusing particularly on the hazardous parafalcine location. RESULTS: The management of subdural empyemas poses different decision-making problems compared to common brain abscesses, urging a more rapid and holistic surgical treatment with minimally invasive approach. Endoscopic aspiration of parafalcine empyema was followed by complete recovery in our patient. CONCLUSIONS: Flexible endoscopy is a promising method to obtain complete pus removal even from loculated collections through a bur hole, avoiding large craniotomies and consequent potential complications.

Third ventriculostomy site as a neuroreceptorial area.

PURPOSE: Endoscopic third ventriculostomy is an established method for treating hydrocephalus. The third ventriculostomy site is considered a safe area that can be disrupted during surgical endoscopic procedures. The question of the clinical consequences of an apparently unavoidable injury to the floor of the third ventricle has been sporadically addressed in the literature. The aim of this study is to describe our anatomical and operative findings during endoscopic procedures performed in fluorescent mode after intravenous fluorescein injection and address the possible role of fluorescein-enhanced visualization of the median eminence as an accessory tool in order to partially spare this functional structure when performing ventriculostomy. METHODS: We prospectively administered intravenously 500 mg of fluorescein sodium in 12 consecutive endoscopic surgery cases. A flexible scope equipped with dual observation modes for both white light and fluorescence was used. Taking into account the position of the basilar apex and the need for a conveniently sized stoma, a perforation area was chosen and dilated using a Fogarty balloon, guided by fluorescein-enhanced visualization of the median eminence. RESULTS: After a mean of 20 s in the fluorescent mode, the fluorescein enhanced the visualization of the median eminence-tuber cinereum complex. In our preliminary experience, by opening the stoma in the fluorescence mode, almost half of the visible median eminence surface can be spared from iatrogenic sacrifice. CONCLUSIONS: Tailoring fluorescence-guided ventriculostomy is a feasible way of trying to preserve the median eminence and may have implications for the site and safety of this common surgical procedure.

The Cerebral Aqueduct Compliance: A Simple Morphometric Model.

BACKGROUND AND OBJECTIVES: This work aimed to identify different configurations of the adytum of the cerebral aqueduct suggesting its safe neuroendoscopic navigation. This concept is intimately connected to the physiological aqueductal dilatability or compliance, which is relatively ignored in the literature. A better knowledge of the extent of physiological aqueductal dilatability might better define the ideal diameter and safer features of dedicated flexible endoscopes. METHODS: The study includes 45 patients operated on using a flexible scope with a 3.9-mm diameter, where the structural elements of the adytum of the cerebral aqueduct are clearly visible. Patients were grouped according to the pathology (colloid cyst/normal anatomy, intraventricular hemorrhage, tetraventricular obstructive hydrocephalus, normal pressure hydrocephalus, and distal membranous aqueductal stenosis). A simple geometrical scheme was applied to the endoscopic anatomy of the aqueductal adytum in relation to the posterior commissure to measure its pathologic deformations. Eventual damages to the aqueduct walls caused by the endoscope were also reported. RESULTS: Proceeding from normal anatomy to hydrocephalic condition, the ratio between the commissure and the aqueductal access area progressively decreases, while the vertex angle increases. Interestingly, the entity of the ependymal damages due to the passage of the endoscope correlates with such measures. CONCLUSION: The cerebral aqueduct, excluding atrophic processes, is provided with a certain degree of dilatability, which we estimate to be around a diameter of 4 mm. This represents the maximum size for a flexible neuroendoscope for a safe aqueductal neuronavigation. The schematic model of the aqueductal adytum as a triangle defines 3 different aqueductal patterns and can be helpful when an intraoperative decision on whether to navigate the aqueduct must be taken.

Hydrocephalus and the First Report of an External Ventriculostomy: The Contributions of Fabrici d'Acquapendente in the Italian Renaissance.

In our historical study, we are unveiling one of the very first surgical treatments of hydrocephalus originally scripted in Latin by Fabrici d'Acquapendente and then transcribed into the French language by Chez Pierre Ravaud. During the European Renaissance, Italian pioneering surgeon Fabricid'Acquapendente illustrated the technique performed at that time. Fabrici described the drainage of fluid for hydrocephalus using the insertion of a cannula. The cannula was kept in place for several days and the fluid was drained slowly and in regulated controlled amounts. Layers of bandage drapes were applied to prevent the leakage of fluid escaping from the wound. Unfortunately, we are missing some significant information regarding the surgical techniques as these were not documented by Fabrici. Although skull trephination was relatively well known, it is unsure whether at the time the cannula was inserted deep within the ventricles. Drainage of the fluid may have still occurred from the extracranial space. Moreover, we are unaware of how long the cannula was kept in place. Nonetheless, Fabrici d'Acquapendente may be considered among the first in Italy and possibly in Europe to lay down the foundations for external ventricular drainage system for hydrocephalus.

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.

Clustering Functional Magnetic Resonance Imaging Time Series in Glioblastoma Characterization: A Review of the Evolution, Applications, and Potentials.

In this paper, we discuss how the clustering analysis technique can be applied to analyze functional magnetic resonance imaging (fMRI) time-series data in the context of glioblastoma (GBM), a highly heterogeneous brain tumor. The precise characterization of GBM is challenging and requires advanced analytical approaches. We have synthesized the existing literature to provide an overview of how clustering algorithms can help identify unique patterns within the dynamics of GBM. Our review shows that the clustering of fMRI time series has great potential for improving the differentiation between various subtypes of GBM, which is pivotal for developing personalized therapeutic strategies. Moreover, this method proves to be effective in capturing temporal changes occurring in GBM, enhancing the monitoring of disease progression and response to treatment. By thoroughly examining and consolidating the current research, this paper contributes to the understanding of how clustering techniques applied to fMRI data can refine the characterization of GBM. This article emphasizes the importance of incorporating cutting-edge data analysis techniques into neuroimaging and neuro-oncology research. By providing a detailed perspective, this approach may guide future investigations and boost the development of tailored therapeutic strategies for GBM.

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.

Neuroendoscopic aspiration of tumors in the posterior third ventricle and aqueduct lumen: a technical update.

BACKGROUND: Small soft ventricular tumors are good candidates for complete removal by a purely endoscopic technique. This approach is particularly interesting for lesions located in the posterior third ventricle and aqueductal lumen. METHODS: We present our method of endoscospic aspiration through direct contact between the tumor and the working channel of a flexible scope. RESULTS: Aspiration without the intermediate use of cannulas is safe and has proved to be effective in the apparently total or partial removal of three soft tumors of different pathologies located in the third ventricle or aqueductal lumen. In one case, a second neuroendoscopy a few months later to repeat endoscopic third ventriculostomy (ETV) offered a unique opportunity to observe the absence of the tumor and the restored anatomy. CONCLUSIONS: Neuroendoscopy provides a safe, effective way to radically resect small soft tumors in these troublesome locations and can be a valuable alternative to microsurgery.

The Roof of the 4th Ventricle Seen From Inside: Endoscopic Anatomic Illustration-A Case Series.

BACKGROUND: The anatomy of the roof of the fourth ventricle has been illustrated in many laboratory investigations, but in vivo reports of the roof anatomy and its variants are still lacking. OBJECTIVE: To describe the topographical anatomy of the roof of the fourth ventricle explored through a transaqueductal approach that overcomes cerebrospinal fluid depletion, displaying in vivo anatomic images possibly quite close to normal physiological conditions. METHODS: We critically reviewed the intraoperative video recordings of our 838 neuroendoscopic procedures, selecting 27 cases of transaqueductal navigation that provided good quality image details of the anatomy of the roof of the fourth ventricle. Twenty-six patients affected by different forms of hydrocephalus were therefore categorized into three groups: Group A: blockage of the aqueduct-aqueductoplasty, Group B: communicating hydrocephalus, and Group C: tetraventricular obstructive hydrocephalus. RESULTS: Group A has shown what the roof of a normal fourth ventricle really looks like albeit the structures seemed overcrowded because of the narrow space. Images from groups B and C paradoxically allowed a more distinct identification of the roof structures flattened by ventricular dilation, making them more comparable with the topography traced on the laboratory microsurgical studies. CONCLUSION: Endoscopic in vivo videos and images provided a novel anatomic view and an in vivo redefinition of the real topography of the roof of the fourth ventricle. The relevant role of cerebrospinal fluid was defined and outlined, as well as the effects of hydrocephalic dilation on some structures on the roof of the fourth ventricle.

Cigarette Smoking and Intracranial Aneurysms: A Pilot Analysis of SNPs in the CYP2A6 Gene in the Italian Population.

BACKGROUND: Cigarette smoking is a modifiable risk factor associated with formation and rupture of intracranial aneurysms (IAs). Cytochrome P450 2A6 (CYP2A6) is the main enzyme implied in catabolism of nicotine and xenobiotics, giving rise to oxidative stress products. Our study investigated the associations between specific single-nucleotide polymorphisms (SNPs) in the CYP2A6 gene and the presence of sporadic IAs in a cluster of Italian patients, as well as their rupture regarding cigarette smoking habit. METHODS: Three hundred and thirty-one Italian patients with sporadic IAs were recruited in a single institution. We recorded data on clinical onset with subarachnoid hemorrhage (SAH) and smoking habit. Genetic analysis was performed with a standard procedure on peripheral blood samples: CYP2A6 ∗1B2, CYP2A6 ∗2, and CYP2A6 ∗14 SNPs were analyzed in the study group along with 150 healthy control subjects. Statistical analysis was conducted according to genetic association study guidelines. RESULTS: In the patient cohort, the frequency of aSAH was significantly higher in current smokers (P < 0.001; OR=17.45), regardless of the pattern of CYP2A6 SNPs. There was a correlation between IA rupture and cigarette smoking in patients with the heterozygous CYP2A6 ∗1B2 allele (P < 0.001; OR=15.47). All patients carrying the heterozygous CYP2A6 ∗14 allele had an aSAH event (100%), regardless of smoking habit, although this correlation was not statistically significant (P = 1). CONCLUSIONS: According to our findings, a cigarette smoker carrying a fully active CYP2A6 enzyme (heterozygous ∗1B2 allele) may have an increased risk of IA rupture compared to those with functionally less active variants: further investigation on a larger sample is needed to verify this result. The role of the heterozygous CYP2A6 ∗14 allele in aSAH is yet to be clarified.

Quantitative Anatomical Studies in Neurosurgery: A Systematic and Critical Review of Research Methods.

BACKGROUND: The anatomy laboratory can provide the ideal setting for the preclinical phase of neurosurgical research. Our purpose is to comprehensively and critically review the preclinical anatomical quantification methods used in cranial neurosurgery. METHODS: A systematic review was conducted following the PRISMA guidelines. The PubMed, Ovid MEDLINE, and Ovid EMBASE databases were searched, yielding 1667 papers. A statistical analysis was performed using R. RESULTS: The included studies were published from 1996 to 2023. The risk of bias assessment indicated high-quality studies. Target exposure was the most studied feature (81.7%), mainly with area quantification (64.9%). The surgical corridor was quantified in 60.9% of studies, more commonly with the quantification of the angle of view (60%). Neuronavigation-based methods benefit from quantifying the surgical pyramid features that define a cranial neurosurgical approach and allowing post-dissection data analyses. Direct measurements might diminish the error that is inherent to navigation methods and are useful to collect a small amount of data. CONCLUSION: Quantifying neurosurgical approaches in the anatomy laboratory provides an objective assessment of the surgical corridor and target exposure. There is currently limited comparability among quantitative neurosurgical anatomy studies; sharing common research methods will provide comparable data that might also be investigated with artificial intelligence methods.