The quantitative comparison between the neuronal network and the cosmic web

We investigate the similarities between two of the most challenging and complex systems in Nature: the network of neuronal cells in the human brain, and the cosmic network of galaxies. We explore the structural, morphological, network properties and the memory capacity of these two fascinating systems, with a quantitative approach. In order to have an homogeneous analysis of both systems, our procedure does not consider the true neural connectivity but an approximation of it, based on simple proximity. The tantalizing degree of similarity that our analysis exposes seems to suggest that the self-organization of both complex systems is likely being shaped by similar principles of network dynamics, despite the radically different scales and processes at play

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

The role of mitotic slippage, USP1-regulated apoptosis, and multiple treatments in the action of temozolomide in glioblastoma multiforme

Background. Temozolomide (TMZ) is a methylating drug that is commonly used in the treatment of glioma. Although many features are still unclear, its general mechanism of action is well described. TMZ induces O6-methylguanine (O6MeG) lesions in DNA, which, in the absence of repair by O6-methylguanine methyltransferase (MGMT), mispair with thymine and start a futile cycle of repair-resynthesis events. The resultant DNA double-strand breaks (DSBs) activate the components of G2 checkpoint, and cells with a 4N DNA content accumulate and remain arrested at the G2/M boundary for several days. Cell death subsequently occurs by senescence, necrosis, or mitotic catastrophe, while apoptosis has been ruled out in many studies. Moreover, the effect of multiple TMZ treatments on G2 arrest and apoptosis induction is not clear. Repair of methylating drug-induced DNA lesions requires monoubiquitination of PCNA and FANCD2. Loss of either protein or inhibition of their monoubiquitination increases drug toxicity. USP1 is a hydrolase that removes monoubiquitin from PCNA and FANCD2, and can potentially play a role in TMZ mechanism of action. Materials and methods. U87, U251 (TMZ-sensitive, low MGMT), and GBM8 (TMZ-resistant, high MGMT) cell lines were used for experiments. The treatment was scheduled with 100μM TMZ for 3 hours for 1, 2, or 3 consecutive days. Cell cycle progression was studied with both FACS-based analysis and a novel time-lapse microscopic real-time analysis using FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator), and apoptosis was measured with FACS-based Annexin V-PI analysis. To address the possible role of USP1 in TMZ action, we examined expression of USP1 at the mRNA levels in expression microarray databases derived from primary GBM. We also used siRNA targeting USP1 to modulate USP1 expression, and studied the effect of USP1 downregulation on TMZ-induced G2 arrest, cell death, and clonogenicity. Results. Compared to single treatment, multiple TMZ treatments cause a significant reduction of clonogenicity in TMZ-sensitive cells and induce a significant increase of apoptosis, particularly in a late stage. However, multiple treatments don’t have any major effect on cell cycle profile. Time-lapse microscopic analysis with FUCCI system showed that TMZ-sensitive glioma cells arrest at the G2 checkpoint for less than 48 hours and, in the presence of an activated G2 checkpoint, they replicate their DNA without cellular division, re-enter the cell cycle at the next G1 phase, and repeat the cycle, ultimately giving rise to polyploid cells. siRNA-mediated suppression of USP1 had no effect on cell cycle progression or the extent of temozolomide-induced G2 arrest. However, while USP1 knockdown alone had minimal effect on cell death, it increased temozolomide-induced loss of clonagenicity both in TMZ-sensitive and TMZ-resistant cells. Further examination of the mechanism of cell death suggested that while control cells, control cells exposed to TMZ, or USP1-suppressed cells rarely underwent apoptotic cell death, temozolomide-treated cells in which USP1 levels were suppressed underwent high rates of apoptosis. Conclusions. The present studies show that TMZ can induce apoptosis in TMZ-sensitive glioma cells, which is visible after 3 days but significant after 7 days. Multiple TMZ treatments don’t affect cell cycle profile, but significantly increase apoptosis. Moreover, time-lapse studies suggest a novel mechanism of action for TMZ, alternative to the one commonly accepted. These results have significant implications for the development of TMZ resistance. Furthermore, rather than sensitizing cells to DNA damaging agents, USP1 appears to suppress latent apoptotic pathways and to protect cells from temozolomide-induced apoptosis. These results identify a new function for USP1 and suggest that suppression of USP1 and/or USP1 controlled pathway may be a means to enhance the cytotoxic potential of temozolomide and to sensitize TMZ-resistant GBM cell

H3 K27M mutation in rosette-forming glioneuronal tumors: a potential diagnostic pitfall

According to the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS), diffuse midline glioma H3 K27-altered is a grade 4 infiltrative glioma that arises from midline anatomical structures and is characterized by the loss of H3 K27me3 and co-occurring H3 K27M mutation or EZHIP overexpression. However, the H3 K27M mutation has also been observed in circumscribed gliomas and glioneuronal tumors arising in midline anatomical structures, which may result in diagnostic pitfalls.Rosette-forming glioneuronal tumor (RGNT) is a CNS WHO grade 1 neoplasm that histologically features neurocytic and glial components and originates in midline anatomical structures.This study aimed to assess whether RGNTs, similar to other midline tumors, may exhibit immunohistochemical loss of H3 K27me3 and harbor the H3 K27M mutation.All seven analyzed RGNTs displayed immunohistochemical loss of H3 K27me3 in all tumor cells or H3 K27me3 mosaic immunostaining. In one case, H3 K27me3 loss was associated with the H3 K27M mutation, whereas the other six cases did not exhibit any H3 mutations or EZHIP overexpression. During a follow-up period of 23 months, the H3 K27M-mutant case remained unchanged in size despite partial resection, indicating that the H3 mutation may not confer higher biological aggressiveness to RGNT.The immunohistochemical loss of H3 K27me3 co-occurring with the H3 K27M mutation may result in the potential misdiagnosis of RGNT, especially in cases of small biopsy specimens consisting of only the glial component

Indoor mobility, frailty, and disability in community-dwelling older adults: a mediation model

The general population, but especially older adults, were forced or encouraged to stay home during the recent COVID-19 pandemic. In this context, indoor mobility (IM, the number of steps performed daily at home) may be informative about the general health status of older adults. The present study aimed at evaluating the relationship between IM, frailty (loss of functional reserve including both physical and psychosocial domains), and disability (loss of autonomy measured as activities of daily life, ADLs) in a sample of community-dwelling Italian older adults. Specifically, the primary objective was to investigate IM and disability differences between robust and frail older adults. The secondary objective was to test if frailty is in the causal sequence between IM and disability, i.e., as a mediator in their relationship. Thirty-two participants (mean age = 70 ± 6 years; 56.2% women) were recruited. Frailty and disability were evaluated using the Tilburg Frailty Indicator and the Groningen Activity Restriction Scale, respectively. IM at home was measured via an Adamo wristwatch (a connected accelerometer). One-way analyses of covariance, controlling for age and gender, showed that robust participants, classified according to a score higher than five points in the Tilburg Frailty Indicator, performed significantly more IM (F1,28 = 4.639; p = 0.04) and presented lower disability grade than frail ones (F1,28 = 4.342; p =0.046). Only physical frailty was a mediator in the relationship between IM and disability (F2,29 = 8.538, p < 0.001), with a fully mediated model (z = -2.073, p < 0.04). Conversely, the total frailty score was not a mediator in the same relationship, but with IM accounted for the variance in disability (F2,29 = 8.538, p < 0.001; R2 = 33.7%). Our results suggested that frail older adults restricted their IM more and presented a higher level of disability compared to robust older adults. Moreover, data suggest that IM reduction may have a negative impact on physical frailty and indirectly increase disability

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

Clinical characteristics of poor-grade aneurysmal subarachnoid hemorrhage treatment

Background: The initial clinical status after aneurysm rupture, whether primary or secondary, determines the final outcome. The most common cause of patient deterioration is a high Hunt and Hess (HH) score, which correlates closely with a high mortality rate. Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is determined as an HH score 4 or 5. The aim of this study was to evaluate the clinical characteristics of poor graded aneurysmal SAH at our institution. Patients and Methods  During the 5-year period, 415 patients with intracranial aneurysm were admitted to our institution. Patients with poor-grade aneurysmal SAH accounted 31.08% ( n  = 132) of the total number of ruptured aneurysms. Interventional treatment was predominantly in the form of surgery, whereas conservative treatment included medication and external ventricular drainage. Final outcome was assessed with a modified Rankin score (mRs). Statistical analysis was performed using SPSS version 23.0 with a significance level set to 5% (α = 0.05). Results  The majority of patients (57.6%) were in the age range from 51 to 69 years. Twenty-five patients (18.9%) had an HH score of 4, whereas 107 patients (81.1%) had an HH score of 5. Depending on the location, the majority of patients ( n  = 43) had an aneurysm on the medial cerebral artery (MCA). The final aneurysm occlusion was performed in 71 patients, of whom 94.36% were treated surgically. A positive outcome (mRs 0-4) was found in 49.25% of patients who underwent primarily surgical, treatment with a mortality of 42.3%. Although the outcome was better in patients with an HH score 4, both groups benefited from surgical treatment. Conclusion  Poor-grade aneurismal SAH is a condition of the middle and older age, with most patients with an HH 5 score and deep comatose state. There was better outcome in patients with an HH score of 4 compared to an HH score of 5 and both groups benefited from surgical treatment, which resulted in a positive outcome in almost 50% of surgically treated patients

Surgical management of adult Brainstem Gliomas: a systematic review and meta-analysis

The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy

Hemodynamics in Ruptured Intracranial Aneurysms

Incidental detection of unruptured intracranial aneurysms (UIA) has increased in the recent years. There is a need in the clinical community to identify those that are prone to rupture and would require preventive treatment. Hemodynamics in cerebral blood vessels plays a key role in the lifetime cycle of intracranial aneurysms (IA). Understanding their initiation, growth, and rupture or stabilization may identify those hemodynamic features that lead to aneurysm instability and rupture. Modeling hemodynamics using computational fluid dynamics (CFD) could aid in understanding the processes in the development of IA. The neurosurgical approach during operation of IA allows direct visualization of the aneurysm sac and its sampling in many cases. Detailed analysis of the quality of the aneurysm wall under the microscope, together with histological assessment of the aneurysm wall and CFD modeling, can help in building complex knowledge on the relationship between the biology of the wall and hemodynamics. Detailed CFD analysis of the rupture point can further strengthen the association between hemodynamics and rupture. In this chapter we summarize current knowledge on CFD and intracranial aneurysms

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