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Background: Brain arteriovenous malformations (AVMs) are challenging vascular lesions. Extensive follow-up studies are necessary to refine the therapeutic algorithm, and to improve long-term survival in these patients. The aim of the study was to assess surgical outcomes, and to evaluate overall long-term mortality in patients treated for brain AVMs. Methods: This retrospective single-center study included 191 patients with brain AVMs, admitted between 2012 and 2022. Clinical and angiographical particularities have been analyzed, to identify factors that might influence early outcome and overall long-term mortality. Results: Out of 79 patients undergoing surgery, 51 had ruptured AVMs with total resection achieved in 68 cases (86.1%). Deep venous drainage was associated with incomplete resection. Female sex, admission modified Rankin Scale (mRS) > 2, and eloquent location were independent predictors of poor outcomes. Multiple venous drainage was associated with a higher risk of worsened early outcome. Eloquent brain region involvement, conservative treatment, increasing age, admission mRS > 2, and comorbidities significantly decrease survival in brain AVM patients. Patients treated with interventional treatments had significantly better survival than the conservatively managed ones, when adjusting for age and admission mRS. Conclusion: The study identified female sex, poor neurologic status on admission and eloquence as independent prognostic factors for a negative outcome after surgery. Patients who received interventional treatment had significantly better survival than patients managed conservatively. We recommend employing tailored, proactive management strategies as they significantly enhance long-term survival in brain AVM patients.

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Background/Objectives: Approximately half of the patients harboring supratentorial brain arterio-venous malformations (stAVMs) present with hemorrhage, and another considerable proportion suffer from epileptic seizures. An important milestone in the management of this vascular pathology is acknowledging their natural history, especially across long periods of time. The aim of this study was to assess the predictive factors for hemorrhage and for epileptic seizures as presenting symptoms in stAVMs. Methods: We retrospectively analyzed patients with stAVMs admitted to our institution between 2012 and 2022 and evaluated predictive factors for hemorrhage and the risk factors associated with epileptic seizures. Results: The cohort included 169 patients, 78 of them (46.2%) presenting with intracerebral hemorrhage (ICH). Seventy-seven (45.5%) patients suffered from epileptic seizures. The annual hemorrhagic rate was 1.28%/year. Unruptured lesions (p = 0.001, OR 3.1, 95% CI 1.6-6.2), superficial venous drainage (p = 0.007, OR 2.7, 95% CI 1.3-5.7) and large nidus size (p = 0.025, OR 4, 95% CI 1.2-13.5) were independently associated with seizures. Among unruptured lesions, superficial venous drainage (OR 2.6, p = 0.036, 95% CI 1.06-6.3) and frontal/temporal/parietal location (OR 2.7, p = 0.040, 95 CI% 1.04-6.9) significantly increased the risk of seizures as a presenting symptom in multivariate analysis. Patients younger than 18 (p = 0.003, OR 4.5, 95% CI 1.6-12.2), those with AVMs < 3 cm (p = 0.03, OR 2, 95% CI 1.07-3.9) or those with deep located AVMs (p = 0.035, OR 2.3, 95% CI 1.06-5.1) presented statistically more often with ICH in multivariate regression. Small size (HR 1.8, 95% CI 1.09-3, p = 0.022) and exclusively deep venous drainage (HR 2.2, 95% CI 1.2-4, p = 0.009) were independent predictors for ICH, in time-dependent birth-to-diagnosis analysis. After shifting the birth-to-diagnosis curve by 10 years, unique arterial feeder demonstrated a positive correlation with ICH presentation as well. Conclusions: Small AVMs, those with exclusively deep venous drainage, unique arterial feeder or deep location may pose higher hemorrhagic risks for the patient, and therapeutic strategies should be tailored accordingly. When managing unruptured brain AVMs, it is important to consider the risk of developing seizures, in addition to the lifelong risk of hemorrhage, in determining the optimal treatment approach for each patient.

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BACKGROUND: Posterior fossa arterio-venous malformations (pfAVMs) are challenging lesions due to the anatomical particularities of the posterior fossa, and the high incidence of hemorrhagic presentation. The two most important goals when treating AVMs are preserving neurological function and preventing rupture, or a second hemorrhage. The aim of this study was to analyze the clinical and imaging features of pfAVMs to identify the factors that influence the prognosis of these patients. METHODS: We conducted a single-center retrospective observational study that included patients treated at our institution with pfAVMs between January 1997 and December 2021. RESULTS: A total of 48 patients were included. A good modified Rankin score (mRS) was observed in 33 cases (69%) at presentation. Thirty-four patients (71%) presented with a ruptured AVM. Out of these, 19 patients (40%) had intraventricular hemorrhage. Microsurgical resection was performed in 33 cases (69%), while in the other cases, the patients opted for conservative management (7 cases, 15%), stereotactic radiosurgery (SRS) (6 cases, 12%), or endovascular treatment (2 cases, 4%). Patients ≤ 30 years old were more prone to hemorrhagic presentation (OR: 5.23; 95% CI: 1.42-17.19; p = 0.024) and this remained an independent risk factor for rupture after multivariate analysis as well (OR: 4.81; 95% CI: 1.07-21.53; p = 0.040). Following multivariate analysis, the only factor independently associated with poor prognosis in the surgically treated subgroup was a poor clinical status (mRS 3-5) at admission (OR: 96.14; 95% CI: 5.15-1793.9; p = 0.002). CONCLUSIONS: Management of posterior fossa AVMs is challenging, and patients who present with ruptured AVMs often have a poor clinical status at admission leading to a poor prognosis. Therefore, proper and timely management of these patients is essential.

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Gliomas are the most common type of cerebral tumors; they occur with increasing incidence in the last decade and have a high rate of mortality. For efficient treatment, fast accurate diagnostic and grading of tumors are imperative. Presently, the grading of tumors is established by histopathological evaluation, which is a time-consuming procedure and relies on the pathologists' experience. Here we propose a supervised machine learning procedure for tumor grading which uses quantitative phase images of unstained tissue samples acquired by digital holographic microscopy. The algorithm is using an extensive set of statistical and texture parameters computed from these images. The procedure has been able to classify six classes of images (normal tissue and five glioma subtypes) and to distinguish between gliomas types from grades II to IV (with the highest sensitivity and specificity for grade II astrocytoma and grade III oligodendroglioma and very good scores in recognizing grade III anaplastic astrocytoma and grade IV glioblastoma). The procedure bolsters clinical diagnostic accuracy, offering a swift and reliable means of tumor characterization and grading, ultimately the enhancing treatment decision-making process.

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GFAPδ, the delta isoform of the glial fibrillary acidic protein, is mainly expressed in the subventricular zone of the brain, together with other neural stem cell markers like nestin. The authors of this paper were among the first that described in detail the expression of GFAPδ and its correlation with malignancy and invasiveness in cerebral astrocytoma. Later, several papers confirmed these findings, showing that the alternative splice variant GFAPδ is overexpressed in glioblastoma (CNS WHO grade 4) compared with lower grade gliomas. Other studies suggested that a high GFAPδ/α ratio is associated with a more malignant and invasive behavior of glioma cells. Moreover, the changing of GFAPδ/α ratio affects the expression of high-malignant genes. It is now suggested that discriminating between predominant GFAP isoforms, GFAPδ or GFAPα, is useful for assessing the malignancy state of astrocytoma, and may even contribute to the classification of gliomas. Therefore, the purpose of this paper is to review the literature with emphasize on the role of GFAPδ as a potential biomarker, and as a possible therapeutic target in glioblastoma.

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Objectives: Brain arteriovenous malformations (AVMs) represent high-flow vascular lesions made up of a complex network of feeding arteries and draining veins interposed by a nidus and without a capillary bed. The management of the AVMs represents a challenge, and the optimal treatment should be considered based on the particularities of each AVM. This paper aims to provide outcome data for the cohort of patients with AVMs that underwent surgical treatment. Methods: A retrospective review of patients who presented with AVMs between 2001 and 2019 was conducted. Patients were included if they underwent surgery, preoperative and postoperative angiographic studies were available. Results: 91 patients were included. The SM grade was 1 in 16 cases (17,6%), 2 in 27 patients (29.7%), 3 in 29 patients (31,9%), 4 in 12 cases (13.2%) and grade 5 in 7 cases (7.7%). In 58 (63.7%) cases the AVMs were ruptured. Complete microsurgical resection was achieved in 82 cases (90.1%). Unruptured AVM (87.9% vs. 63.8% for ruptured AVMs; p = 0.015), low-grade AVM (86% vs. 60.4% for grade III-V AVMs; p = 0.006) and cortical location (79.5% vs. 30.8% for deep AVM; p < 0.0001) were the factors associated with a good outcome on mRS scale. Conclusions: Microsurgical resection is the curative treatment for AVMs and offers a good functional outcome if selection criteria are met.

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Cancer is one of the most frequent and devastating diseases. Previous reports have shown that radio and chemo-resistant cancer stem cell (CSC) population is primarily responsible for cancer recurrences after radiotherapy and chemotherapy. Other studies demonstrated that Lissencephaly-1 (LIS1) protein, also known as platelet activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1), a dynein-binding protein involved in neural stem cell division, plays a crucial role in maintaining CSC population in hematological malignancies. Moreover, one recent report demonstrated that LIS1 gene is preferentially expressed in CD133+ glioblastoma cells and may have also an important role in regulating CD133+ CSC in glioblastoma. The hypothesis of this paper is that LIS1 plays a key role in maintaining CD133+ CSC population in various solid cancers by orientating the cell division plane through an interaction with dynein and therefore controlling the stem cell fate regulatory mechanism. As CD133+ CSC population is responsible for radio- and chemo-resistance, which finally determines the cancer recurrences and metastases, identifying the molecular mechanisms which regulate the CD133+ CSC population represents a major target for cancer research. Given the structure of LIS1, which contains WD40 repeat domain, small peptide inhibitors could be used to alter its function. Therefore, the impact of confirming this hypothesis is significant because LIS1 may become an important molecular target for future adjuvant anticancer therapies directed against radio- and chemo-resistant CSC population.

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Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome.

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