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Distal anterior cerebral aneurysm (DACA) represents 4% of intracranial aneurysms. Two treatment modalities are available: microsurgery and endovascular therapy (EVT). To compare the results between microsurgery and EVT in a modern French cohort. A multicenter retrospective cohort study of 3 French neurosurgical units was carried out from January 1, 2015, to December 31, 2020. All participants were adult patients who required treatment for a ruptured or unruptured DACA aneurysm. A total of 69 patients were included; 16 patients (23.2%) were treated by microsurgery and 53 (76.8%) were treated by EVT. Thirty-one patients (44.9%) had ruptured aneurysms. The complication rate was low, with 1 death and 1 symptomatic ischemia. There was no difference in complications between microsurgery and EVT (P = 0.22). The number of retreatments was higher in EVT (15% vs. 0%) but not significantly (P = 0.18). In the specific subgroup of DACA, both treatment modalities are effective in ruptured and unruptured aneurysms, with a low rate of complications. Retreatment may be more frequent in EVT but it does not lead to more complications. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to better characterise clinical presentation, management and outcome in infants and children with brain abscess.Methods: The authors conducted a retrospective, multicentre study in two national reference centres over a 25-year period (1992-2017). During this period, 116 children and 28 infants (age <1 year) with brain abscess were treated.Results: The median age at diagnosis was 101.5 (range: 13-213) months in children and 1 (0-11) month in infants. Significant differences were observed between children and infants. The most common predisposing factor was meningitis in infants (64% of cases vs 3% in children), while it was otolaryngology-related infection in children (31% of cases vs 3.6% in infants). Infants presented more frequently with fever and meningism compared with children. 115 patients were treated with aspiration and 11 with excision. Reoperation was required in 29 children vs 1 infant. The overall mortality rate was 4% (3.4% for children, 7.1% for infants). At 3-month follow-up, the outcome was favourable in 86% of children vs in 68% of infants.Conclusion: There is a clear difference between children and infants with brain abscess in terms of predisposing factors, causative organisms and outcome. Despite surgical drainage and directed antibiotic therapy, 25% of patients with brain abscess require reoperation. Mortality is improved compared with historical series; however, long-term morbidity is significant particularly in the infant population. [ABSTRACT FROM AUTHOR]

Purpose: Temozolomide (TMZ) is known to induce thrombocytopenia but no early predictive test has yet been clearly established. The aim of the study was to retrospectively identify and validate a threshold of early platelet variation predicting TMZ-induced thrombocytopenia during the TMZ phase in patients treated according to the Stupp protocol for glioblastoma.Methods: A training set was used to analyze variations in platelet count occurring from the first week (W1) to week 6 (W6) during radiotherapy. Our aim was to identify the most relevant platelet decrease associated with TMZ-induced thrombocytopenia ≤ 100 G/L at day 28 during the TMZ phase. The performance of the threshold was confirmed in an independent validation set.Results: Overall, 147 patients were included, 85 and 62 in the training and validation sets, respectively. Twenty-seven patients (18%) experienced at least one TMZ-induced thrombocytopenia in the TMZ phase. A platelet decrease at W6 ≥ 35% (∆W6 ≥ 35%) was identified as the best predictive variation with an AUC of 0.83, a sensitivity of 65%, and a specificity of 96%. In the validation set, ∆W6 ≥ 35% platelet variation was identified as an independent marker of TMZ-induced thrombocytopenia during the TMZ phase (OR 15.23 (95% CI 3.5-107.5)) corresponding to sensitivity of 77% (66-87%), specificity of 73% (62-84%), a positive predictive value of 42% (29-54%), and a negative predictive value of 92% (86-99%).Conclusion: Platelet decrease at W6 ≥ 35% during the RT-TMZ phase is an early and simple predictive marker of clinically relevant TMZ-induced thrombocytopenia during TMZ maintenance. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to explore metabolic remodeling in plasma and tissue samples in patients with glioblastoma through an integrated targeted and untargeted metabolomics-based strategy. We report phospholipids, sphingomyelins, acylcarnitines, and acylglycerols as key impaired metabolic classes in glioblastoma. (1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension. The mean survival is between 15 to 17 months. Given this aggressive prognosis, there is an urgent need for a better understanding of the underlying mechanisms of glioblastoma to unveil new diagnostic strategies and therapeutic targets through a deeper understanding of its biology. (2) Methods: To systematically address this issue, we performed targeted and untargeted metabolomics-based investigations on both tissue and plasma samples from patients with glioblastoma. (3) Results: This study revealed 176 differentially expressed lipids and metabolites, 148 in plasma and 28 in tissue samples. Main biochemical classes include phospholipids, acylcarnitines, sphingomyelins, and triacylglycerols. Functional analyses revealed deep metabolic remodeling in glioblastoma lipids and energy substrates, which unveils the major role of lipids in tumor progression by modulating its own environment. (4) Conclusions: Overall, our study demonstrates in situ and systemic metabolic rewiring in glioblastoma that could shed light on its underlying biological plasticity and progression to inform diagnosis and/or therapeutic strategies. [ABSTRACT FROM AUTHOR]

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common malignant brain tumor in adults. The current management relies on surgical resection and adjuvant radiotherapy and chemotherapy. Despite advances in our understanding of glioblastoma onset, we are still faced with an increased incidence, an altered quality of life and a poor prognosis, its relapse and a median overall survival of 15 months. For the past few years, the understanding of glioblastoma physiopathology has experienced an exponential acceleration and yielded significant insights and new treatments perspectives. In this review, through an original R-based literature analysis, we summarize the clinical presentation, current standards of care and outcomes in patients diagnosed with glioblastoma. We also present the recent advances and perspectives regarding pathophysiological bases as well as new therapeutic approaches such as cancer vaccination and personalized treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common malignant primary brain tumor in adults. Glioblastoma accounts for 2 to 3 cases per 100,000 persons in North America and Europe. Glioblastoma classification is now based on histopathological and molecular features including isocitrate dehydrogenase (IDH) mutations. At the end of the 2000s, genome-wide sequencing of glioblastoma identified recurrent somatic genetic alterations involved in oncogenesis. Among them, the alterations in the promoter region of the telomerase reverse transcriptase (TERTp) gene are highly recurrent and occur in 70% to 80% of all glioblastomas, including glioblastoma IDH wild type and glioblastoma IDH mutated. This review focuses on recent advances related to physiopathological mechanisms, diagnosis, and clinical implications. Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth. The aim of this systematic review is to provide an overview of the available data concerning TERT alterations and glioblastoma in terms of incidence, physiopathological understanding, and potential therapeutic implications. [ABSTRACT FROM AUTHOR]

Germinal matrix-intraventricular-intraparenchymal hemorrhage (GMH-IVH-IPH) is a major complication of very preterm births before 32 weeks of gestation (WG). Despite progress in clinical management, its incidence remains high before 27 WG. In addition, severe complications may occur such as post-hemorrhagic hydrocephalus and/or periventricular intraparenchymal hemorrhage. IVH is strongly associated with subsequent neurodevelopmental disabilities. For this review, an automated literature search and a clustering approach were applied to allow efficient filtering as well as topic clusters identification. We used a programmatic literature search for research articles related to intraventricular hemorrhage in preterms that were published between January 1990 and February 2020. Two queries ((Intraventricular hemorrhage) AND (preterm)) were used in PubMed. This search resulted in 1093 articles. The data manual curation left 368 documents that formed 12 clusters. The presentation and discussion of the clusters provide a comprehensive overview of existing data on the pathogenesis, complications, neuroprotection and biomarkers of GMH-IVH-IPH in very preterm infants. Clinicians should consider that the GMH-IVH-IPH pathogenesis is mainly due to developmental immaturity of the germinal matrix and cerebral autoregulation impairment. New multiomics investigations of intraventricular hemorrhage could foster the development of predictive biomarkers for the benefit of very preterm newborns. [ABSTRACT FROM AUTHOR]

Brain developmental lesions are a devastating consequence of prenatal alcohol exposure (PAE). We recently showed that PAE affects cortical vascular development with major effects on angiogenesis and endothelial cell survival. The underlying molecular mechanisms of these effects remain poorly understood. This study aimed at characterizing the ethanol exposure impact on the autophagic process in brain microvessels in human fetuses with fetal alcohol syndrome (FAS) and in a PAE mouse model. Our results indicate that PAE induces an increase of autophagic vacuole number in human fetal and neonatal mouse brain cortical microvessels. Subsequently, ex vivo studies using green fluorescent protein (GFP)-LC3 mouse microvessel preparations revealed that ethanol treatment alters autophagy in endothelial cells. Primary cultures of mouse brain microvascular endothelial cells were used to characterize the underlying molecular mechanisms. LC3 and p62 protein levels were significantly increased in endothelial cells treated with 50 mM ethanol. The increase of autophagic vacuole number may be due to excessive autophagosome formation associated with the partial inhibition of the mammalian target of rapamycin pathway upon ethanol exposure. In addition, the progression from autophagosomes to autolysosomes, which was monitored using autophagic flux inhibitors and mRFP-EGFP vector, showed a decrease in the autolysosome number. Besides, a decrease in the Rab7 protein level was observed that may underlie the impairment of autophagosome-lysosome fusion. In addition, our results showed that ethanol-induced cell death is likely to be mediated by decreased mitochondrial integrity and release of apoptosis-inducing factor. Interestingly, incubation of cultured cells with rapamycin prevented ethanol effects on autophagic flux, ethanol-induced cell death and vascular plasticity. Taken together, these results are consistent with autophagy dysregulation in cortical microvessels upon ethanol exposure, which could contribute to the defects in angiogenesis observed in patients with FAS. Moreover, our results suggest that rapamycin represents a potential therapeutic strategy to reduce PAE-related brain developmental disorders.