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1.
Neurobiol Dis ; 196: 106521, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697575

RESUMO

BACKGROUND: Lesion network mapping (LNM) is a popular framework to assess clinical syndromes following brain injury. The classical approach involves embedding lesions from patients into a normative functional connectome and using the corresponding functional maps as proxies for disconnections. However, previous studies indicated limited predictive power of this approach in behavioral deficits. We hypothesized similarly low predictiveness for overall survival (OS) in glioblastoma (GBM). METHODS: A retrospective dataset of patients with GBM was included (n = 99). Lesion masks were registered in the normative space to compute disconnectivity maps. The brain functional normative connectome consisted in data from 173 healthy subjects obtained from the Human Connectome Project. A modified version of the LNM was then applied to core regions of GBM masks. Linear regression, classification, and principal component (PCA) analyses were conducted to explore the relationship between disconnectivity and OS. OS was considered both as continuous and categorical (low, intermediate, and high survival) variable. RESULTS: The results revealed no significant associations between OS and network disconnection strength when analyzed at both voxel-wise and classification levels. Moreover, patients stratified into different OS groups did not exhibit significant differences in network connectivity patterns. The spatial similarity among the first PCA of network maps for each OS group suggested a lack of distinctive network patterns associated with survival duration. CONCLUSIONS: Compared with indirect structural measures, functional indirect mapping does not provide significant predictive power for OS in patients with GBM. These findings are consistent with previous research that demonstrated the limitations of indirect functional measures in predicting clinical outcomes, underscoring the need for more comprehensive methodologies and a deeper understanding of the factors influencing clinical outcomes in this challenging disease.


Assuntos
Neoplasias Encefálicas , Conectoma , Glioblastoma , Imageamento por Ressonância Magnética , Humanos , Glioblastoma/mortalidade , Glioblastoma/diagnóstico por imagem , Glioblastoma/fisiopatologia , Masculino , Feminino , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/diagnóstico por imagem , Pessoa de Meia-Idade , Conectoma/métodos , Estudos Retrospectivos , Adulto , Idoso , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia
2.
Front Neurol ; 14: 1175576, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37409023

RESUMO

Background: Resting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain's functional topological organization and glioblastoma (GBM) location. Furthermore, we assessed whether GBM distribution across these networks was associated with overall survival (OS). Materials and methods: We included patients with histopathological diagnosis of IDH-wildtype GBM, presurgical MRI and survival data. For each patient, we recorded clinical-prognostic variables. GBM core and edema were segmented and normalized to a standard space. Pre-existing functional connectivity-based atlases were used to define network parcellations: 17 GMNs and 12 WMNs were considered in particular. We computed the percentage of lesion overlap with GMNs and WMNs, both for core and edema. Differences between overlap percentages were assessed through descriptive statistics, ANOVA, post-hoc tests, Pearson's correlation tests and canonical correlations. Multiple linear and non-linear regression tests were employed to explore relationships with OS. Results: 99 patients were included (70 males, mean age 62 years). The most involved GMNs included ventral somatomotor, salient ventral attention and default-mode networks; the most involved WMNs were ventral frontoparietal tracts, deep frontal white matter, and superior longitudinal fasciculus system. Superior longitudinal fasciculus system and dorsal frontoparietal tracts were significantly more included in the edema (p < 0.001). 5 main patterns of GBM core distribution across functional networks were found, while edema localization was less classifiable. ANOVA showed significant differences between mean overlap percentages, separately for GMNs and WMNs (p-values<0.0001). Core-N12 overlap predicts higher OS, although its inclusion does not increase the explained OS variance. Discussion and conclusion: Both GBM core and edema preferentially overlap with specific GMNs and WMNs, especially associative networks, and GBM core follows five main distribution patterns. Some inter-related GMNs and WMNs were co-lesioned by GBM, suggesting that GBM distribution is not independent of the brain's structural and functional organization. Although the involvement of ventral frontoparietal tracts (N12) seems to have some role in predicting survival, network-topology information is overall scarcely informative about OS. fMRI-based approaches may more effectively demonstrate the effects of GBM on brain networks and survival.

3.
Int J Cancer ; 151(12): 2265-2277, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36054818

RESUMO

The immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) is mainly driven by tumor-associated macrophages (TAMs). We explored whether their sustained iron metabolism and immunosuppressive activity were correlated, and whether blocking the central enzyme of the heme catabolism pathway, heme oxygenase-1 (HO-1), could reverse their tolerogenic activity. To this end, we investigated iron metabolism in bone marrow-derived macrophages (BMDMs) isolated from GBM specimens and in in vitro-derived macrophages (Mφ) from healthy donor (HD) blood monocytes. We found that HO-1 inhibition abrogated the immunosuppressive activity of both BMDMs and Mφ, and that immunosuppression requires both cell-to-cell contact and soluble factors, as HO-1 inhibition abolished IL-10 release, and significantly reduced STAT3 activation as well as PD-L1 expression. Interestingly, not only did HO-1 inhibition downregulate IDO1 and ARG-2 gene expression, but also reduced IDO1 enzymatic activity. Moreover, T cell activation status affected PD-L1 expression and IDO1 activity, which were upregulated in the presence of activated, but not resting, T cells. Our results highlight the crucial role of HO-1 in the immunosuppressive activity of macrophages in the GBM TME and demonstrate the feasibility of reprogramming them as an alternative therapeutic strategy for restoring immune surveillance.


Assuntos
Glioblastoma , Heme Oxigenase-1 , Macrófagos Associados a Tumor , Humanos , Antígeno B7-H1/metabolismo , Glioblastoma/patologia , Heme , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Terapia de Imunossupressão , Interleucina-10 , Ferro , Microambiente Tumoral
4.
Curr Oncol ; 29(5): 3472-3488, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35621670

RESUMO

Glioblastomas with multiple foci at presentation (mGBMs) account for 2-35% of all GBMs. mGBMs have limited existing data and no standardized treatment. This study aims to determine their incidence, demographic and clinical features, outcome, and prognostic factors in terms of overall survival. We performed a monocentric retrospective study, reviewing patients treated at the Istituto Oncologico Veneto. Inclusion criteria were: new diagnosis of GBM and presence of multiple lesions on pre-treatment MRI. ECOG PS was used to evaluate clinical condition, RANO criteria for radiological assessment, and CTCAE v5.0 for treatment-related adverse events. The incidence of newly diagnosed mGBM was 7.2% and the study population consisted of 98 patients. Median age was 63 years, M:F ratio of 1.8:1, and a surgical approach was undertaken in 73 patients (mostly partial resection). MGMT was methylated in 47.5%, and 82 patients received active oncological treatment (65.9% radiotherapy plus temozolomide (RT + TMZ)). The disease control rate with RT + TMZ was 63%. Median OS of the entire study population was 10.2 months (95% CI 6.6-13.8), and median PFS was 4.2 months (95% CI 3.2-5.2). The ECOG PS, the extent of resection, and the RT + TMZ were significant prognostic factors in the univariate analysis for OS, but only the RT + TMZ was a significant independent OS predictor in the multivariate analysis (HR = 3.1, 95% IC 1.3-7.7, p = 0.014). The incidence of mGBM is not rare. RT + TMZ is confirmed to be an independent prognostic factor for survival and a safe and effective treatment. When feasible, RT + TMZ should be considered as a possible first-line treatment. The role of the extent of resection is still unclear.


Assuntos
Neoplasias Encefálicas , Dacarbazina , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Dacarbazina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Temozolomida/uso terapêutico
5.
Global Spine J ; 12(4): 719-731, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33887971

RESUMO

STUDY DESIGN: Case series and systematic review of the Literature. OBJECTIVES: Pharyngo-esophageal perforation (PEP) is a rare, life-threatening complication of anterior cervical spine surgery (ACSS). Best management of these patients remains poorly defined. The aim of this study is to present our experience with this entity and to perform a systematic Literature review to better clarify the appropriate treatment of these patients. METHODS: Patients referred to our center for PEP following ACSS (January 2002-December 2018) were identified from our database. Moreover, an extensive review of the English Literature was conducted according to the 2009 PRISMA guidelines. RESULTS: Twelve patients were referred to our Institution for PEP following ACSS. Indications for ACSS were trauma (n = 10), vertebral metastases (n = 1) and disc herniation (n = 1). All patients underwent hardware placement at the time of ACSS. There were 6 early and 6 delayed PEP. Surgical treatment was performed in 11 patients with total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement, anatomical suture of the fistula and suture line reinforcement with myoplasty. Complete resolution of PEP was observed in 6 patients. Five patients experienced PEP persistence, requiring further surgical management in 2 cases. At a median follow-up of 18.8 months, all patients exhibited permanent resolution of the perforation. CONCLUSIONS: PEP following ACSS is a rare but dreadful complication. Partial or total removal of the fixation devices, direct suture of the esophageal defect and coverage with tissue flaps seems to be an effective surgical approach in these patients.

6.
Front Immunol ; 12: 809826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069595

RESUMO

Background: Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods: Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results: Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient's outcome. Conclusions: This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use.


Assuntos
Biomarcadores Tumorais/sangue , Glioma/sangue , Glioma/diagnóstico , Células Mieloides/imunologia , Células Mieloides/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arginase/sangue , Antígeno B7-H1/sangue , Feminino , Glioma/etiologia , Humanos , Hospedeiro Imunocomprometido , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Fator de Transcrição STAT3/sangue , Adulto Jovem
7.
Neurosurg Focus ; 49(6): E9, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33260134

RESUMO

OBJECTIVE: The purpose of this study was to analyze the effect of the coronavirus disease 2019 (COVID-19) outbreak and of the subsequent lockdown on the neurosurgical services of the Veneto region in Italy compared to the previous 4 years. METHODS: A survey was conducted in all 6 neurosurgical departments in the Veneto region to collect data about surgical, inpatient care and endovascular procedures during the month of March for each year from 2016 to 2020. Safety measures to avoid infection from SARS-CoV-2 and any COVID-19 cases reported among neurosurgical patients or staff members were considered. RESULTS: The mean number of neurosurgical admissions for the month of March over the 2016-2019 period was 663, whereas in March 2020 admissions decreased by 42%. Emergency admissions decreased by 23%. The average number of neurosurgical procedures was 697, and declined by 30% (range -10% to -51% in individual centers). Emergency procedures decreased in the same period by 23%. Subarachnoid hemorrhage and spontaneous intracerebral hemorrhage both decreased in Veneto-by 25% and 22%, respectively. Coiling for unruptured aneurysm, coiling for ruptured aneurysm, and surgery for ruptured aneurysm or arteriovenous malformation diminished by 49%, 27%, and 78%, respectively. Endovascular procedures for acute ischemic stroke (AIS) increased by 33% in 2020 (28 procedures in total). There was a slight decrease (8%) in brain tumor surgeries. Neurosurgical admissions decreased by 25% and 35% for head trauma and spinal trauma, respectively, while surgical procedures for head trauma diminished by 19% and procedures for spinal trauma declined by 26%. Admissions and surgical treatments for degenerative spine were halved. Eleven healthcare workers and 8 patients were infected in the acute phase of the pandemic. CONCLUSIONS: This multicenter study describes the effects of a COVID-19 outbreak on neurosurgical activities in a vast region in Italy. Remodulation of neurosurgical activities has resulted in a significant reduction of elective and emergency surgeries compared to previous years. Most likely this is a combined result of cancellation of elective and postponable surgeries, increase of conservative management, increase in social restrictions, and in patients' fear of accessing hospitals. Curiously, only endovascular procedures for AIS have increased, possibly due to reduced physical activity or increased thrombosis in SARS-CoV-2. The confounding effect of thrombectomy increase over time cannot be excluded. No conclusion can be drawn on AIS incidence. Active monitoring with nasopharyngeal swabs, wearing face masks, and using separate pathways for infected patients reduce the risk of infection.


Assuntos
COVID-19/epidemiologia , Surtos de Doenças , Pessoal de Saúde/normas , Procedimentos Neurocirúrgicos/normas , Inquéritos e Questionários , COVID-19/prevenção & controle , Surtos de Doenças/prevenção & controle , Pessoal de Saúde/tendências , Humanos , Itália/epidemiologia , Procedimentos Neurocirúrgicos/tendências
8.
Sci Rep ; 10(1): 7614, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376983

RESUMO

Cerebrovascular surgery can benefit from an intraoperative system that conducts continuous monitoring of cerebral blood flow (CBF). Such a system must be handy, non-invasive, and directly integrated into the surgical workflow. None of the currently available techniques, considered alone, meets all these criteria. Here, we introduce the SurgeON™ system: a newly developed non-invasive modular tool which transmits high-resolution Laser Speckle Contrast Imaging (LSCI) directly onto the eyepiece of the surgical microscope. In preclinical rodent and rabbit models, we show that this system enabled the detection of acute perfusion changes as well as the recording of temporal response patterns and degrees of flow changes in various microvascular settings, such as middle cerebral artery occlusion, femoral artery clipping, and complete or incomplete cortical vessel cautery. During these procedures, a real-time visualization of vasculature and CBF was available in high spatial resolution through the eyepiece as a direct overlay on the live morphological view of the surgical field. Upon comparison with indocyanine green angiography videoangiography (ICG-VA) imaging, also operable via SurgeON, we found that direct-LSCI can produce greater information than ICG-VA and that continuous display of data is advantageous for performing immediate LSCI-guided adjustments in real time.


Assuntos
Circulação Cerebrovascular , Lasers , Imagem Molecular/instrumentação , Monitorização Intraoperatória/instrumentação , Animais , Ratos , Fatores de Tempo
9.
J Neurosci Methods ; 315: 6-13, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30630001

RESUMO

BACKGROUND: Peripheral nerve injury is often followed by a highly variable recovery process with respect to both rapidity and efficacy. Identifying post-nerve injury phenomena is key to assessing the merit and timing of surgery as well as to tracking nerve recovery postoperatively. Diffusion Tensor Imaging (DTI) has been investigated in the clinical and research settings as a noninvasive technique to both assess and monitor each patient's unique case of peripheral nerve damage. NEW METHOD: We identify a MRI-suitable marker for tracking the exact site of either nerve injury or coaptation following surgical repair to aid with DTI analysis. RESULTS: Due to artefact and disruption of tractography, silver wire and microvascular clips were not suitable markers. AxoGuard®, 4-0 vicryl suture, and 10-0 polyamide suture, although detectable, did not produce a signal easily distinguished from post-surgical changes. Silicone was easily identifiable and stable in both the acute and delayed time points, exhibited negligible impact on DTI parameters, and possessed geometry to prevent nerve strangulation. COMPARISON WITH EXISTING METHOD: Prior studies have not assessed the efficacy of other markers nor have they assessed silicone for potential artefact with DTI parameter analysis. Furthermore, this work demonstrates the reliability and compatibility of silicone in the delayed postoperative time period and includes its unique imaging appearance on high-resolution 11.7 MRI. CONCLUSION: Semi-cylindrical silicone tubing can be used as a safe, reliable, and readily available radiological marker to visualize and monitor a region of interest on a rodent's peripheral nerve for aiding assessments with diffusion tensor imaging.


Assuntos
Imagem de Tensor de Difusão/instrumentação , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Nervos Periféricos/diagnóstico por imagem , Próteses e Implantes , Equipamentos e Provisões para Radiação , Animais , Imagem de Tensor de Difusão/métodos , Modelos Animais de Doenças , Feminino , Ratos Endogâmicos F344 , Silicones
10.
World Neurosurg ; 122: e856-e863, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30391771

RESUMO

OBJECTIVE: Fluorescence-guided glioblastoma surgery is an intraoperative technique developed in recent years. Two main compounds have been used so far: 5-amilovelulinic acid (5-ALA) and fluorescein sodium (Fl-Na). Despite a large amount of literature on both techniques, few data are available on the use of both compounds in the same patient. METHODS: Three consecutive patients affected by a newly diagnosed glioblastoma underwent surgical resection using both 5-ALA and Fl-Na. 5-ALA was orally administered 3 hours before induction of anesthesia at a dosage of 20 mg/kg, whereas fluorescein was intravenously administered at induction of anesthesia at a dosage of 4 mg/kg. Tumor resection was carried out combining these fluorophores. At tumor borders, multiple samples were collected, and fluorescent pattern of each sample was registered. Samples were then analyzed by a neuropathologist blinded for intraoperative fluorescence findings. RESULTS: Eighteen samples were analyzed. At tumor margin, bright pink fluorescence was highly indicative of residual tumor (positive predictive value [PPV], 94%), and it was superior to faint pink and fluorescein (PPVs, 89% and 87%, respectively). The gradual reduction of pink fluorescence warned of the risk of gradually entering healthy tissue (specificity of 67% compared with 33% with fluorescein). Using 5-ALA, detecting no fluorescence was highly suggestive of healthy tissue (negative predictive value of 100% compared with 50% with fluorescence). CONCLUSIONS: In our experience with 3 patients, the 2 techniques presented different advantages and limitations in specific steps of tumor resection, showing complementary properties. Larger studies are mandatory to investigate the synergistic use of both techniques.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Fluoresceína/administração & dosagem , Glioblastoma/diagnóstico por imagem , Monitorização Intraoperatória/métodos , Imagem Óptica/métodos , Ácido Aminolevulínico/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Feminino , Fluoresceína/metabolismo , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/metabolismo , Glioblastoma/metabolismo , Glioblastoma/cirurgia , Humanos , Masculino , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/metabolismo
11.
World Neurosurg ; 113: e336-e344, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29452324

RESUMO

OBJECTIVE: The aim of this study is to report data on a multimodal monitoring strategy based on the intraoperative use of neurophysiological monitoring, flowmetry by microflow probe, and intraoperative indocyanine green video angiography (ICG-VA) during microsurgical clipping of intracranial aneurysms. METHODS: This retrospective analysis was performed on 85 consecutive patients undergoing clipping of 96 intracranial aneurysms with the present monitoring strategy. Patient outcomes were evaluated by assessing rate of aneurysm exclusion and postoperative occurrence of ischemic injury. Intraoperative data for the strategy in addition to changes in each monitoring technique depending on aneurysm features were reported. RESULTS: Complete aneurysm exclusion was achieved in 98.9% of cases. Postoperative symptomatic ischemic injury was recorded in 2.08% aneurysms. Clip repositioning occurred in 40.6% of cases: because of motor evoked potential (MEP) decrease in 9.3%, flowmetry in 22.91%, and ICG-VA in 8.3% of treated aneurysms (1.05% after ICG injection, 7.4% after the squeezing maneuver). The role of each technique differed according to aneurysm features; flowmetry alterations occurred more frequently in distal than in proximal aneurysms (P = 0.0001) and in atherosclerotic aneurysms (P = 0.0001). MEP impairment occurred more often in proximal aneurysms (P < 0.05). ICG-VA disclosed remnant aneurysms mainly in atherosclerotic aneurysms (P < 0.05); only one false negative remnant neck was recorded with a negative predictive value of 98.8%. CONCLUSIONS: Microsurgical clipping assisted by a multimodal monitoring strategy achieved a high rate of aneurysm exclusion with low morbidity in our series. Our data show that the 3 techniques used in our strategy were complementary and that a monitoring strategy can be tailored to aneurysm features.


Assuntos
Angiografia Cerebral/métodos , Circulação Cerebrovascular , Aneurisma Intracraniano/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Microcirurgia/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Cirurgia Vídeoassistida , Aneurisma Roto/cirurgia , Isquemia Encefálica/etiologia , Hemorragia Cerebral/etiologia , Corantes , Potencial Evocado Motor , Humanos , Verde de Indocianina , Monitorização Neurofisiológica Intraoperatória/instrumentação , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Reologia , Instrumentos Cirúrgicos
12.
Sci Rep ; 7(1): 14978, 2017 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-29097800

RESUMO

Tumor progression, limited efficacy of current standard treatments, and the rise in patient mortality are associated with gene expression caused by the synergistic action of intratumoral hypoxia and HIF-1α activation. For this reason, recent investigations have focused on HIF-targeting therapeutic agents, with encouraging preclinical and clinical results in solid tumors. Here we describe the efficacy of a HIF-1α inhibitor, Acriflavine, and demonstrate its potency against brain cancer. This safe antibacterial dye induces cell death and apoptosis in several glioma cell lines, targets HIF-1α-mediated pathways, and decreases the level of PGK1, VEGF and HIF-1α in vitro and in vivo. Administered locally via biodegradable polymers, Acriflavine provides significant benefits in survival resulting in nearly 100% long term survival, confirmed by MRI and histological analyses. This study reports preclinical evidence that this safe, small molecule can contribute to brain tumor therapy and highlights the significance of HIF-1α-targeting molecules.


Assuntos
Acriflavina/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Corantes Fluorescentes/uso terapêutico , Glioma/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Acriflavina/administração & dosagem , Acriflavina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/farmacologia , Glioma/metabolismo , Glioma/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos Endogâmicos F344
13.
Neurosurg Rev ; 39(4): 565-73, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26846668

RESUMO

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which may rarely occurs as a complication of supratentorial procedures, and it shows a typical bleeding pattern defined "the zebra sign." However, its pathophysiology still remains unknown. We performed a comprehensive review collecting all cases of RCH after supratentorial craniotomies reported in literature in order to identify the most frequently associated procedures and the possible risk factors. We assessed percentages of incidence and 95 % confidence intervals of all demographic, neuroradiological, and clinical features of the patients. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 49 articles reporting 209 patients with a mean age of 49.09 ± 17.07 years and a male/female ratio 130/77. A RCH was more frequently reported as a complication of supratentorial craniotomies for intracranial aneurysms, tumors debulking, and lobectomies. In the majority of cases, RCH occurrence was associated with impairment of consciousness, although some patients remained asymptomatic or showed only slight cerebellar signs. Coagulation disorders, perioperative cerebrospinal fluid drainage, hypertension, and seizures were the most frequently reported risk factors. Zebra sign was the most common bleeding pattern, being observed in about 65 % out of the cases, followed by parenchymal hematoma and mixed hemorrhage in similar percentages. A multivariate analysis showed that symptomatic onset and intake of antiplatelets/anticoagulants within a week from surgery were independent predictors of poor outcome. However, about 75 % out of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless in the event of the occurrence of complications.


Assuntos
Hemorragia Cerebral/cirurgia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Hemorragias Intracranianas/cirurgia , Complicações Pós-Operatórias/cirurgia , Hemorragia Pós-Operatória/cirurgia , Hemorragia Cerebral/diagnóstico , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Humanos , Hemorragias Intracranianas/diagnóstico , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/etiologia , Resultado do Tratamento
14.
Neurosurg Rev ; 39(3): 369-76, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26627110

RESUMO

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which can be rarely observed as a complication of spine surgery. As well as for RCH reported after supratentorial procedures, it shows a characteristic bleeding pattern defined "zebra sign". Nowadays, RCH pathophysiology still remains unknown. We performed a comprehensive review, collecting all cases of RCH after spine surgery reported in literature in order to identify the procedures most frequently associated with RCH and the possible risk factors. We assessed percentages of incidence and 95 % confidence interval of all demographic, neuroradiological, and clinical features. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 44 articles reporting 57 patients with mean age of 57.6 ± 13.9 years and a male/female ratio of 23/34. A RCH was more frequently reported as a complication of decompressive procedures for spinal canal stenosis, particularly when associated with instrumented fusion, followed by spinal tumor debulking and disc herniation removal. In the majority of cases, RCH occurrence was characterized by progressive impairment of consciousness, whereas some patients complained non-specific symptoms. Coagulation disorders, hypertension, and placement of postoperative subfascial drainages were the most frequently reported risk factors. The occurrence of intraoperative dural lesions was described in about 93 % of patients. Zebra sign was the most common bleeding pattern (about 43 % of cases) followed by parenchymal hematoma (37.5 %) and mixed hemorrhage (about 20 %). Impairment of consciousness at clinical onset and intake of anticoagulants/antiplatelets appeared associated with poor outcome at univariate analysis. However, more than 75 % of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless of the occurrence of complications.


Assuntos
Doenças Cerebelares/cirurgia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/cirurgia , Descompressão Cirúrgica , Hemorragias Intracranianas/cirurgia , Complicações Pós-Operatórias/cirurgia , Humanos , Hemorragias Intracranianas/complicações , Fatores de Risco
15.
World Neurosurg ; 84(3): 741-50, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25957724

RESUMO

OBJECTIVE: Despite technical surgical advance, the ultimate management of midline anterior skull base meningiomas remains to be defined. Open transcranial surgery is usually the first treatment option for large meningiomas, while less invasive techniques such as endoscopic surgery or radiosurgery might represent an alternative to open microsurgery for smaller lesions. The aim of our study is to investigate the outcome of open transcranial microsurgery in the resection of small (<35 mm) meningiomas of the midline anterior cranial base. METHODS: Clinical and surgical data from 43 patients affected by small midline anterior skull base meningiomas operated via an open transcranial approach were retrospectively reviewed. RESULTS: The tumor diameter on its major axis ranged from 12 to 35 mm, with a mean diameter of 28 mm. Gross total resection (Simpson grades I-II) was achieved in 100% of cases through a pterional approach. Postoperative overall morbidity was 9%. It was 3% among patients <70 years. No mortality was reported. Postoperative visual outcome was significantly associated with preoperative visual performance (P = 0.02), but not with preoperative optic nerve compression as detected by magnetic resonance imaging (P = 0.116). Age >70 years was associated with postoperative visual impairment, although not significantly (P = 0.06). Visual function was preserved or improved in 95% of cases, in 100% of patients <70 years, and in 71% of patients with preoperative visual impairment. CONCLUSIONS: In our experience, open transcranial surgery proved safe and effective for midline anterior skull base meningiomas smaller than 35 mm in all patients <70 years and in patients >70 years without preoperative visual deficit. Our data are consistent with the literature. Conversely, the standard of treatment for the subgroup of patients >70 years with preoperative visual deficit has not yet been defined. This specific subgroup of patients offers a topic for further investigation.


Assuntos
Meningioma/cirurgia , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Base do Crânio/cirurgia , Base do Crânio/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Meningioma/patologia , Microcirurgia/mortalidade , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/psicologia , Procedimentos Neurocirúrgicos/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/psicologia , Estudos Retrospectivos , Base do Crânio/patologia , Neoplasias da Base do Crânio/patologia , Resultado do Tratamento , Visão Ocular
16.
Clin Neurol Neurosurg ; 116: 35-40, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24309149

RESUMO

OBJECTIVES: The purpose of this work is to assess the surgical and clinical outcome of intracranial aneurysm clipping performed combining the assistance of green indocyanine videoangiography (ICGV) and ultrasonic perivascular microflow probe. PATIENTS AND METHODS: Data from patients affected with intracranial aneurysms who underwent microsurgical clipping assisted by both techniques between May 2012 and April 2013 were retrospectively evaluated. RESULTS: 26 patients with 34 aneurysms (25 unruptured) were enrolled. In a total of 11 aneurysms (32%), the vascular clip needed repositioning, since either the post-clipping microprobe assessment detected a significant flow reduction of the explored vessels (8 cases, 23%) or ICGV identified a residual non-obliterated aneurysm (3 cases, 9%). A second clip repositioning was required in 3 cases (9%) because of dome remnant showed with ICGV. In all cases, final microprobe and ICGV assessments showed a complete exclusion of the aneurysm, without evidence of vascular flow impairment. Postoperatively, 1 patient (3%) presented a residual neck aneurysm. No permanent morbidity was reported. CONCLUSION: With the limits of our small case series, our results testify that the presented approach may provide high exclusion rate in the treatment of cerebral aneurysm with very low morbidity in selected patients.


Assuntos
Angiografia Digital , Verde de Indocianina , Aneurisma Intracraniano/cirurgia , Microcirurgia , Procedimentos Neurocirúrgicos , Instrumentos Cirúrgicos , Adulto , Idoso , Angiografia Cerebral/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Ultrassonografia
18.
Acta Neurochir (Wien) ; 155(3): 415-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23307335

RESUMO

BACKGROUND: Maximal safe resection is the goal of correct surgical treatment of parasagittal meningiomas, and it is intimately related to the venous anatomy both near and directly involved by the tumor. Indocyanine green videoangiography (ICGV) has already been advocated as an intra-operative resourceful technique in brain tumor surgery for the identification of vessels. The aim of this study was to investigate the role of ICGV in surgery of parasagittal meningiomas occluding the superior sagittal sinus (SSS). METHOD: In this study, we prospectively analyzed clinical, radiological and intra-operative findings of patients affected by parasagittal meningioma occluding the SSS, who underwent ICGV assisted-surgery. Radiological diagnosis of complete SSS occlusion was pre-operatively established in all cases. ICGV was performed before dural opening, before and during tumor resection, at the end of the procedure. RESULTS: Five patients were included in our study. In all cases, ICGV guided dural opening, tumor resection, and venous management. The venous collateral pathway was easily identified and preserved in all cases. Radical resection was achieved in four cases. Surgery was uneventful in all cases. CONCLUSIONS: Despite the small number of patients, our study shows that ICG videoangiography could play a crucial role in guiding surgery of parasagittal meningioma occluding the SSS. Further studies are needed to define the role of this technique on functional and oncological outcome of these patients.


Assuntos
Angiografia Cerebral/métodos , Verde de Indocianina , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Neuronavegação/métodos , Seio Sagital Superior/cirurgia , Cirurgia Vídeoassistida/métodos , Adulto , Idoso , Angiografia Digital , Craniotomia/métodos , Feminino , Humanos , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Angiografia por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Microcirurgia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X
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