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1.
Brain Lang ; 200: 104710, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739187

RESUMO

This study used voxel-based lesion-symptom mapping to examine the cortical and white matter regions associated with language production impairments in a sample of 63 preoperative tumour patients. We identified four cognitive functions considered crucial for spoken language production: semantic-to-lexical mapping (selecting the appropriate lexical label for the intended concept); phonological encoding (retrieving the word's phonological form); articulatory-motor planning (programming the articulatory motor movements); and goal-driven language selection (exerting top-down control over the words selected for production). Each participant received a score estimating their competence on each function. We then mapped the region(s) where pathology was significantly associated with low scores. For semantic-to-lexical mapping, the critical map encompassed portions of the left posterior middle and inferior temporal gyri, extending into posterior fusiform gyrus, overlapping substantially with the territory of the inferior longitudinal fasciculus. For phonological encoding, the map encompassed the left inferior parietal lobe and posterior middle temporal gyrus, overlapping with the territory of the inferior longitudinal and posterior arcuate fasciculi. For articulatory-motor planning, the map encompassed parts of the left frontal pole, frontal operculum, and inferior frontal gyrus, and overlapped with the territory of the frontal aslant tract. Finally, the map for goal-driven language selection encompassed the left frontal pole and the anterior cingulate cortex. We compare our findings with those from other neuropsychological samples, and conclude that the study of tumour patients offers evidence that complements that available from other populations.


Assuntos
Mapeamento Encefálico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Transtornos da Linguagem/patologia , Transtornos da Linguagem/fisiopatologia , Fala/fisiologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/complicações , Feminino , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Humanos , Transtornos da Linguagem/complicações , Masculino , Pessoa de Meia-Idade , Semântica , Lobo Temporal/patologia , Lobo Temporal/fisiopatologia , Substância Branca/patologia , Substância Branca/fisiopatologia , Adulto Jovem
2.
World Neurosurg ; 133: 55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562962

RESUMO

Laughter has a major role in daily social interactions; consequently, its biologic bases have been previously studied. Nevertheless, its cerebral representation remains unclear. The most accepted hypothesis has postulated that laughter has 2 components: mirth, related to the temporal and frontal neocortical areas, and motor aspect, related to the limbic system and brainstem. Furthermore, in prior studies, laughter has been elicited during electric stimulation with depth electrodes in the supplementary motor area and the cingulum. This Video 1 reports resection of a right superior frontal gyrus diffuse astrocytoma (isocitrate dehydrogenase mutant, World Health Organization grade II) with awake intraoperative electric cortical and subcortical stimulation mapping. Diffusion tensor imaging (DTI) tractography, including all the tracts in relation to the tumor, was obtained preoperatively and postoperatively. Stimulation of the cingulum medially and inferiorly to the tumor elicited a patient's smile and laugh without mirth or merriment. Also, this point correlated with the reconstructed cingulum in the intraoperatively navigated DTI tractography. In conclusion, these findings support the anatomic subdivision of the laughter's mechanism and the role of the cingulum in its motor component. Furthermore, smiles and laughter could be useful functional landmarks to identify the cingulum during subcortical mapping. Although it remains unclear whether pursuing resection beyond this point would have caused permanent postoperative deficits, considering laughter's role in social interaction and other emotion-processing functions associated with the cingulum, in the future it could be potentially considered a functional limit of the resection of intrinsic tumors.


Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Giro do Cíngulo/fisiopatologia , Riso/fisiologia , Sorriso/fisiologia , Astrocitoma/patologia , Astrocitoma/fisiopatologia , Mapeamento Encefálico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Estimulação Elétrica , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Lobo Frontal/cirurgia , Humanos
4.
BMJ Case Rep ; 12(8)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451471

RESUMO

A 68-year-old man, with a history of non-Hodgkin's lymphoma in remission, was admitted for homonymous hemianopsia, headaches and subacute progressive cognitive decline. Imaging revealed brain infarcts and angiography suggested vasculitis. A brain biopsy, however, revealed an intravascular large B-cell lymphoma (IVLBL). Central nervous system (CNS) vasculitis and IVLBL of the brain are extremely rare diseases that can have an almost identical clinical presentation. Angiographic findings are very similar but usually are reported as compatible with vasculitis. Brain biopsy or a random skin biopsy are crucial in diagnosing IVLBL as the accuracy of angiographic findings for CNS vasculitis is low.


Assuntos
Neoplasias Encefálicas , Encéfalo , Linfoma Difuso de Grandes Células B , Vasculite do Sistema Nervoso Central/diagnóstico , Idoso , Biópsia/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Diagnóstico Diferencial , Cefaleia/diagnóstico , Cefaleia/etiologia , Hemianopsia/diagnóstico , Hemianopsia/etiologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/fisiopatologia , Masculino
5.
Top Magn Reson Imaging ; 28(4): 197-204, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31385899

RESUMO

Functional MRI is a reliable, noninvasive technique which allows spatial mapping of the various functions like sensorimotor, language and vision in the brain. This is of immense help to the neurosurgeon in presurgical planning and intraoperative navigation in order to identify and preserve eloquent areas of the brain and minimize post-surgical neurological deficits. Using this technique in children pose unique challenges. This article discusses some of these challenges and how they can be overcome in successful application of this technique in pediatric patients.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Humanos , Pediatria/métodos , Cuidados Pré-Operatórios/métodos
6.
Cir Cir ; 87(4): 459-465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264990

RESUMO

Introduction: Diffuse gliomas are brain neoplasms with an infiltrative growing pattern to cortical and subcortical structures, frequently adjacent to eloquent areas; direct cortical and subcortical stimulation in awake craniotomy is a useful tool to achieve a gross total resection with the least neurological deficit. Presentation of Cases: A 24 years old male presented with tonic-clonic seizures. The magnetic resonance imaging (MRI) showed a left parietal glioma. Awake craniotomy was performed using neuronavigation system and brain mapping with cortical and subcortical stimulation. Functional areas were found at the rostral margin of the tumor; however, the rest of the tumor was almost totally resected. Patient was discharged without neurological deficit. A 29 years old male presented in two occasions generalized tonic-clonic seizures, with right hemiparesis. The MRI showed a left parietal glioma. Awake craniotomy was performed using neuronavigation system and brain mapping with cortical and subcortical stimulation, achieving a gross total resection. Patient was discharged without neurological deficit. Conclusions: Awake craniotomy with brain mapping by cortical and subcortical stimulation and neuronavigation, are the best assets to treat diffuse gliomas and achieve a gross total resection, ensuring the major disease-free interval and preserving the function of eloquent areas.


Assuntos
Mapeamento Encefálico , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Glioma/fisiopatologia , Glioma/cirurgia , Vigília , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Craniotomia/métodos , Intervalo Livre de Doença , Glioma/diagnóstico por imagem , Glioma/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Neuronavegação/métodos , Convulsões/etiologia , Adulto Jovem
7.
BMJ Case Rep ; 12(7)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352376

RESUMO

A 52-year-old woman with cervical cancer stage IIB presented with altered sensorium and breathlessness to the emergency room 5 months after completing primary chemoradiotherapy, which was diagnosed as aspiration pneumonia. She was found to have cerebellar metastases with additional frontal, occipital, and temporal lobe lesions. She had no evidence of extracranial disease. She received supportive care and palliative whole brain radiotherapy and was asymptomatic at 6 months following radiotherapy. Median reported survival is 8-13 months.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma de Células Escamosas/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/terapia , Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Confusão , Dispneia , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Paliativos , Resultado do Tratamento , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/terapia
8.
Medicine (Baltimore) ; 98(25): e16012, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232933

RESUMO

To evaluate the diagnostic value of combining 3D arterial spin labeling (ASL) and stretched-exponential diffusion model in grading of gliomas.A total of 72 patients with histo-pathology proved gliomas (34 low-grade, 38 high-grade) were included in this study. 3D ASL and multi-b diffusion weighted imaging (DWI) images were retrospectively analyzed. The ASL and DWI parameters-tumor blood flow (TBF), distributed diffusion coefficient (DDC), and diffusion heterogeneity α were compared between high-grade and low-grade groups and P < .05 was regarded as statistically significant. TBF was also normalized to the corresponding values in contralateral mirror regions of interest (ROI) (M-TBF), normal grey matter (G-TBF), and white matter (W-TBF) and were compared between high and low-grade tumors.TBF values were significantly higher in high-grade gliomas (P < .001). In stretched-exponential model, the α value of low-grade gliomas showed significant higher than high-grade gliomas group (P < .001), but there was no difference of DDC (P > .05). When TBF values were normalized to contralateral mirror ROI, normal grey matter and white matter, G-TBF showed the highest sensitivity and specificity for differentiation high-grade and low-grade gliomas. The area under area under curve (AUC) of G-TBF and α for glioma grading were 0.926 and 0.892, respectively. The area under AUC of the G-TBF combination with α was 0.960 and corresponding sensitivity and specificity were 94.1% and 98.7%.The combination of 3D ASL and stretched-exponential model parameters can be used to differentiate high-grade and low-grade gliomas. Combination G-TBF and α value can obtain best diagnostic performance.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Glioma/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Adulto , Idoso , Área Sob a Curva , Velocidade do Fluxo Sanguíneo , Neoplasias Encefálicas/fisiopatologia , Circulação Cerebrovascular , Feminino , Glioma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Gradação de Tumores , Estudos Retrospectivos , Sensibilidade e Especificidade , Marcadores de Spin
9.
Mol Med Rep ; 20(2): 1149-1156, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173217

RESUMO

Cell division cycle associated 7 like (CDCA7L) belongs to the JPO protein family, recently identified as a target gene of c­Myc and is frequently dysregulated in multiple cancers. However, to the best of our knowledge, no studies to date have been carried out to investigate the functions of CDCA7L in glioma. Thus, in this study, the expression level of CDCA7L and its association with the prognosis in glioma were detected through the TCGA database. The mRNA expression levels of CDCA7L in glioblastoma (GBM) tissues and normal brain tissues were detected by RT­qPCR and western blot analysis. To explore the role of CDCA7L in glioma, CDCA7L siRNA was constructed and transfected into U87 glioma cells. The expression levels of CDCA7L and cyclin D1 (CCND1) in glioma U87 cells following transfection with CDCA7L siRNA were measured by RT­qPCR and western blot analysis. CCK­8, colony formation, EdU and Transwell assays were used to measure the effects of CDCA7L on U87 cell proliferation, and flow cytometry was used to monitor the changes in the cell cycle following transfection with CDCA7L siRNA. Xenograft tumors were examined in vivo for the carcinogenic effects, as well as the mechanisms and prognostic value of CDCA7L in glioma tissues. The results revealed that CDCA7L was highly expressed in human GBM tissues, and a high expression of CDCA7L was associated with a poor prognosis of glioma patients through the TCGA database. We demonstrated that CDCA7L was highly expressed in human GBM tissues and 3 glioma cell lines. The downregulation CDCA7L expression significantly inhibited the proliferation and colony formation ability of U87 cells by blocking cell cycle progression in the G0/G1 phase. In addition, we found that the mRNA and protein levels of CCND1 were markedly decreased following transfection with CDCA7L siRNA compared with NC siRNA in vitro. The downregulation CDCA7L expression reduced the number of invading cells. Consistent with the results of the in vitro assays, the xenograft assay, immunohistochemistry (IHC) assay and western blot analysis demonstrated that, in response to CDCA7L inhibition, tumor growth was inhibited, Ki­67 and CCND1 expression levels were decreased in vivo. On the whole, the results of the current study indicate that CDCA7L is highly expressed in human glioma tissues and that a high CDCA7L expression predicts a poor prognosis of glioma patients. CDCA7L promotes glioma U87 cell growth through CCND1.


Assuntos
Neoplasias Encefálicas/genética , Proliferação de Células , Ciclina D1/genética , Glioblastoma/genética , Proteínas Repressoras/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/fisiopatologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Glioblastoma/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Genes Dev ; 33(11-12): 591-609, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31160393

RESUMO

Glioblastoma ranks among the most lethal of all human cancers. Glioblastomas display striking cellular heterogeneity, with stem-like glioblastoma stem cells (GSCs) at the apex. Although the original identification of GSCs dates back more than a decade, the purification and characterization of GSCs remains challenging. Despite these challenges, the evidence that GSCs play important roles in tumor growth and response to therapy has grown. Like normal stem cells, GSCs are functionally defined and distinguished from their differentiated tumor progeny at core transcriptional, epigenetic, and metabolic regulatory levels, suggesting that no single therapeutic modality will be universally effective against a heterogenous GSC population. Glioblastomas induce a systemic immunosuppression with mixed responses to oncoimmunologic modalities, suggesting the potential for augmentation of response with a deeper consideration of GSCs. Unfortunately, the GSC literature has been complicated by frequent use of inferior cell lines and a lack of proper functional analyses. Collectively, glioblastoma offers a reliable cancer to study cancer stem cells to better model the human disease and inform improved biologic understanding and design of novel therapeutics.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Glioblastoma/patologia , Glioblastoma/fisiopatologia , Células-Tronco Neoplásicas/fisiologia , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Diferenciação Celular , Epigênese Genética , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Microambiente Tumoral
11.
Brain Struct Funct ; 224(6): 2167-2181, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168738

RESUMO

With the objective to investigate the role of the insula in recognizing emotion, we performed direct electrical stimulation over the anterior insular cortex during awake surgery while simultaneously delivering an emotional sensitivity task. We registered 18 consecutive patients with brain tumors associated with the insular lobe, who were undergoing tumor resection. An emotional sensitivity task was employed to measure the patients' ability to recognize emotions from facial expressions before, during, and after awake surgery. Furthermore, we performed voxel-based lesion symptom mapping (VLSM) to identify the association between relevant brain lesions and emotion recognition. When we performed direct electrical stimulation over the anterior insular cortex during awake surgery, the results showed that the ability to recognize anger was significantly enhanced with the presence of anterior insular stimulation (p < 0.05). Comparing the performance in the emotional sensitivity task before and after surgery, the performance in the anger condition became worse (p < 0.01), but became better in the sadness condition after surgery (p < 0.01). In the case of anger recognition, lower scores in the correct response index were associated with lesions involving the left insula in the VLSM study. Direct electrical stimulation over the anterior insular cortex enhanced anger recognition in patients with insular tumors. In contrast, accuracy of anger recognition was significantly reduced, and sadness was improved, when the performance of emotional sensitivity was compared pre- and post-surgery. Our findings suggest that the insular cortex is involved in changes in emotion recognition, including anger and sadness recognition by modulating arousal level that is closely connected with interoception.


Assuntos
Neoplasias Encefálicas/patologia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adolescente , Adulto , Idoso , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/fisiopatologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/cirurgia , Expressão Facial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Vigília/fisiologia , Adulto Jovem
12.
Comput Methods Programs Biomed ; 175: 35-43, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104713

RESUMO

BACKGROUND AND OBJECTIVES: An accurate and real-time model of soft tissue is critical for surgical simulation for which a user interacts haptically and visually with simulated patients. This paper focuses on the real-time deformation model of brain tissue for the interactive surgical simulation, such as neurosurgical simulation. METHODS: A new Finite Element Method (FEM) based model with constraints is proposed for the brain tissue in neurosurgical simulation. A new energy function of constraints characterizing the interaction between the virtual instrument and the soft tissue is incorporated into the optimization problem derived from the implicit integration scheme. Distance and permanent deformation constraints are introduced to describe the interaction in the convexity meningioma dissection and hemostasis. The proposed model is particularly suitable for GPU-based computing, making it possible to achieve real-time performance. RESULTS AND CONCLUSIONS: Simulation results show that the simulated soft tissue exhibits the behaviors of adhesion and permanent deformation under the constraints. Experiments show that the proposed model is able to converge to the exact solution of the implicit Euler method after 96 iterations. The proposed model was implemented in the development of a neurosurgical simulator, in which surgical procedures such as dissection of convexity meningioma and hemostasis were simulated.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Meningioma/diagnóstico por imagem , Algoritmos , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Simulação por Computador , Análise de Elementos Finitos , Hemostasia , Humanos , Fígado/diagnóstico por imagem , Fígado/fisiopatologia , Fígado/cirurgia , Meningioma/fisiopatologia , Meningioma/cirurgia , Modelos Cardiovasculares , Neurocirurgia , Reprodutibilidade dos Testes , Software , Realidade Virtual
13.
BMJ Case Rep ; 12(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068345

RESUMO

Intracranial lipoma is a relatively rare benign lesion. Many are incidental findings; however, some others may present with headache, hydrocephalus or other neurological symptoms; thus, correct diagnosis of this condition is important. These lesions are of high signal intensity on T2-weighted MRI and especially those close to cerebrospinal fluid (CSF) spaces, can easily be overlooked in the background of high signal intensity of CSF. Here, we present a case of tectal lipoma, with subsequent severe hydrocephalus and absence of septum pellucidum which was initially misinterpreted as a form of holoprosencephaly, due to inadequate attention to T1-weighted images.


Assuntos
Neoplasias Encefálicas/diagnóstico , Holoprosencefalia/patologia , Hidrocefalia/patologia , Lipoma/diagnóstico , Imagem por Ressonância Magnética , Derivação Ventriculoperitoneal , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/terapia , Pré-Escolar , Diagnóstico Diferencial , Holoprosencefalia/diagnóstico por imagem , Holoprosencefalia/terapia , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/terapia , Lipoma/fisiopatologia , Lipoma/terapia , Masculino , Teto do Mesencéfalo/patologia , Resultado do Tratamento
14.
J Neurooncol ; 143(3): 483-493, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31073964

RESUMO

PURPOSE: After treatment, pediatric brain tumor survivors (PBTS) face emotional and behavioral challenges, perhaps due to tumor or treatment-related changes in brain structures involved in emotion regulation, including those with fronto-limbic connections. We hypothesized that relative to healthy controls (HCs), PBTS would exhibit greater difficulties with behavior and emotional functioning, and display reduced mean fractional anisotropy (mFA) in white matter tracts with fronto-limbic connections including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF). We further predicted that mFA would account for variance in the relationship between group and emotional/behavioral outcome. METHODS: Eleven 8-16 year old PBTS and 14 HCs underwent MRI, including diffusion tensor imaging to assess white matter microstructure. Tractography quantified mFA of selected tracts. Parents rated children's emotional and behavioral functioning. RESULTS: Compared to HCs, caregivers of PBTS reported poorer behavioral regulation and greater internalizing and externalizing symptoms. Relative to HCs, PBTS had lower mFA within the bilateral CB, IFOF, and UF (ds = 0.59-1.15). Across groups, several medium-to-large correlations linked tract mFA and increased internalizing, externalizing, and poor behavioral regulation. Tract mFA also accounted for significant variance in the group-outcome association. CONCLUSIONS: Reduced mFA in fronto-limbic associated tracts may be associated with reduced behavioral regulation following pediatric brain tumor. PBTS with treatment known to impact white matter may be most susceptible. Research with larger, longitudinal samples should clarify this relationship, allow for multiple mediators across time, and consider factors like tumor and treatment type.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Sobreviventes de Câncer/estatística & dados numéricos , Emoções/fisiologia , Lobo Frontal/patologia , Sistema Límbico/patologia , Comportamento Problema , Substância Branca/patologia , Adolescente , Anisotropia , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/psicologia , Estudos de Casos e Controles , Criança , Imagem de Tensor de Difusão/métodos , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
15.
Math Biosci Eng ; 16(4): 2795-2810, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31137238

RESUMO

This work investigates the mechano-biological features of cells cultured in monolayers in response to different osmotic conditions. In-vitro experiments have been performed to quantify the long-term effects of prolonged osmotic stresses on the morphology and proliferation capacity of glioblastoma cells. The experimental results highlight that both hypotonic and hypertonic conditions affect the proliferative rate of glioblastoma cells on different cell cycle phases. Moreover, glioblastoma cells in hypertonic conditions display a flattened and elongated shape. The latter effect is explained using a nonlinear elastic model for the single cell. Due to a crossover between the free energy contributions related to the cytosol and the cytoskeletal fibers, a critical osmotic stress determines a morphological transition from a uniformly compressed to an elongated shape.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Glioblastoma/fisiopatologia , Pressão Osmótica , Astrócitos/metabolismo , Divisão Celular , Linhagem Celular Tumoral , Proliferação de Células , Simulação por Computador , Citoesqueleto/metabolismo , Dextranos/química , Elasticidade , Humanos , Microscopia , Modelos Biológicos , Osmose , Pressão , Esferoides Celulares/citologia , Estresse Fisiológico , Resultado do Tratamento
16.
Seizure ; 69: 283-289, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141785

RESUMO

PURPOSE: To examine the occurrence of glioma-related preoperative seizures (GPS) and post-operative seizure control (PSC) with respect to patients characteristics including five commonly tested tumor molecular markers (TMMs). METHODS: A single-center retrospective cohort study of patients with glioma evaluated at the Mayo Clinic, Florida between 2016 and 2018. RESULTS: 68 adult patients (mean age = 51-years, 45-males) were included. 46 patients had GPS. 57 patients underwent intra-operative electrocorticography during awake craniotomy-assisted glioma resection. All patients underwent glioma resection (53, gross-total resection) with histologies of pilocytic astrocytoma (n = 2), diffuse astrocytoma (n = 4), oligodendroglioma (n = 14), anaplastic astrocytoma (n = 16), anaplastic oligodendroglioma (n = 1), and glioblastoma (n = 31). 31 (67%) patients had PSC (median follow-up = 14.5 months; IQR = 7-16.5 months). IDH1 mutation (IDH1mut) was present in 32, ARTX retention in 53, MGMT gene promotor methylation in 15, 1p/19q co-deletion in 15, and over-expression of p53 in 19 patients. Patients with IDH1mut were more likely to have GPS (p = 0.037) and PSC (p = 0.035) compared to patients with IDH1 wild-type. Patients with MGMT gene promoter methylation were also likely to have PSC (p = 0.032). GPS or PSC did not differ by age, sex, extent of surgery, glioma grade, location, and histopathological subtype, p53 expression, ARTX retention, or 1p/19q co-deletion status. CONCLUSIONS: GPS and PSC may be associated with IDH1 mutation and MGMT gene promoter methylation status but not other glioma characteristics including tumor grade, location, or histopathology. Prospective studies with larger sample size are needed to clarify the exact mechanisms of GPS and PSC by the various TMMs to identify new treatment targets.


Assuntos
Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Convulsões/genética , Convulsões/terapia , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Metilação de DNA , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Feminino , Glioma/fisiopatologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/genética , Complicações Pós-Operatórias/terapia , Período Pré-Operatório , Regiões Promotoras Genéticas , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/fisiopatologia , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
17.
Anesthesiology ; 131(1): 36-45, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31094751

RESUMO

BACKGROUND: Midazolam has been found to exacerbate or unmask limb motor dysfunction in patients with brain tumors. This study aimed to determine whether the exacerbated upper limb motor-sensory deficits are mediated through benzodiazepine sites by demonstrating reversibility by flumazenil in patients with gliomas in eloquent areas. METHODS: This was an interventional, parallel assignment, nonrandomized trial. Study subjects were admitted in the operating room. Patients with supratentorial eloquent area gliomas and volunteers of similar age without neurologic disease were sedated with midazolam, but still responsive and cooperative. Motor and sensory functions for upper extremities were evaluated by the Nine-Hole Peg Test before and after midazolam, as well as after flumazenil reversal. RESULTS: Thirty-two cases were included: 15 in the glioma group and 17 in the control group. The total dose of midazolam and flumazenil were comparable between the groups. In the glioma group, the times to task completion after midazolam in the contralateral hand (P = 0.001) and ipsilateral hand (P = 0.002) were 26.5 (95% CI, 11.3 to 41.7) and 13.7 (95% CI, 5.0 to 22.4) seconds slower than baseline, respectively. After flumazenil reversal, the contralateral hand (P = 0.99) and ipsilateral hand (P = 0.187) performed 1.2 (95% CI, -3.3 to 5.8) and 1.5 (95% CI, -0.5 to 3.5) seconds slower than baseline, respectively. In the control group, the dominant (P < 0.001) and nondominant hand (P = 0.006) were 2.9 (95% CI, 1.4 to 4.3) and 1.7 (95% CI, 0.5 to 2.9) seconds slower than baseline, respectively. After flumazenil, the dominant hand (P = 0.99) and nondominant hand (P = 0.019) performed 0.2 (95% CI, -0.7 to 1.0) and 1.3 (95% CI, -0.2 to 2.4) seconds faster than baseline, respectively. CONCLUSIONS: In patients with eloquent area gliomas, mild sedation with midazolam induced motor coordination deficits in upper limbs. This deficit was almost completely reversed by the benzodiazepine antagonist flumazenil, suggesting that this is a reversible abnormality linked to occupation of the receptor by midazolam.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Flumazenil/farmacologia , Glioma/fisiopatologia , Midazolam/farmacologia , Transtornos Motores/tratamento farmacológico , Extremidade Superior/fisiopatologia , Adulto , Neoplasias Encefálicas/complicações , Feminino , Moduladores GABAérgicos/farmacologia , Glioma/complicações , Humanos , Hipnóticos e Sedativos/farmacologia , Masculino , Pessoa de Meia-Idade , Transtornos Motores/induzido quimicamente , Transtornos Motores/fisiopatologia
18.
J Vet Med Sci ; 81(8): 1205-1210, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30982789

RESUMO

The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period as prognostic indicators in dogs. Data from 17 dogs which were scheduled to undergo elective craniotomy for brain tumor surgery from 2009 to 2012 were included. Of these, five (29.4%) died during 14 days after the surgery because of respiratory failure following pneumonia (n=2), euthanasia due to difficulty in treatment of status epilepticus (n=1), tumor-bed hematoma (n=1), and unknown reason (n=1). In the 12 surviving dogs, neurological signs were improved or resolved at discharge. All dogs were administered midazolam and droperidol-fentanyl as premedication. General anesthesia was induced using propofol maintained on isoflurane and oxygen. Direct ICP was obtained via a Codman Microsensor strain gauge transducer. ICP hypertension (>13 mmHg) measured after 15 min of recovery from the moment after discontinuation of anesthesia by turning off the vaporizer dial was associated with poor prognosis (odds ratio, 20.00; 95% confidence interval, 1.39-287.60, P=0.028). This suggests that intracranial pressure influences the postoperative mortality rate in dogs undergoing brain tumor surgery.


Assuntos
Neoplasias Encefálicas/veterinária , Craniotomia/veterinária , Doenças do Cão/fisiopatologia , Doenças do Cão/cirurgia , Hipertensão Intracraniana/veterinária , Anestesia Geral , Animais , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Cães , Hipertensão Intracraniana/mortalidade , Hipertensão Intracraniana/cirurgia , Período Pós-Operatório , Prognóstico
19.
Nat Biomed Eng ; 3(3): 230-245, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30948807

RESUMO

The compression of brain tissue by a tumour mass is believed to be a major cause of the clinical symptoms seen in patients with brain cancer. However, the biological consequences of these physical stresses on brain tissue are unknown. Here, via imaging studies in patients and by using mouse models of human brain tumours, we show that a subgroup of primary and metastatic brain tumours, classified as nodular on the basis of their growth pattern, exert solid stress on the surrounding brain tissue, causing a decrease in local vascular perfusion as well as neuronal death and impaired function. We demonstrate a causal link between solid stress and neurological dysfunction by applying and removing cerebral compression, which respectively mimic the mechanics of tumour growth and of surgical resection. We also show that, in mice, treatment with lithium reduces solid-stress-induced neuronal death and improves motor coordination. Our findings indicate that brain-tumour-generated solid stress impairs neurological function in patients, and that lithium as a therapeutic intervention could counter these effects.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/fisiopatologia , Lítio/uso terapêutico , Estresse Fisiológico , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Humanos , Camundongos Nus , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Perfusão
20.
PLoS One ; 14(4): e0215400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31017934

RESUMO

OBJECTIVE: To assess the inter-technique agreement of relative cerebral blood volume (rCBV) measurements obtained using T1- and T2*-perfusion MRI on 3T scanner in glioma patients. METHODS: A total of 49 adult patients with gliomas underwent both on T1- and T2*-perfusion in the same scanning session, and rCBV maps were estimated using both methods. For the quantitative analysis; Two independent observers recorded the rCBV values from the tumor as well as contralateral brain tissue from both T1- and T2*-perfusion. Inter-observer and inter-technique rCBV measurement agreement were determined by using 95% Bland-Altman limits of agreement and intra-class correlation coefficient (ICC) statistics. RESULTS: Qualitative analysis of the conventional and perfusion images showed that 16/49 (32.65%) tumors showed high susceptibility, and in these patients T2*-perfusion maps were suboptimal. Bland-Altman plots revealed an agreement between two independent observers recorded rCBV values for both T1- and T2*-perfusion. The ICC demonstrated strong agreement between rCBV values recorded by two observers for both T2* (ICC = 0.96, p = 0.040) and T1 (ICC = 0.97, p = 0.026) perfusion and similarly, good agreement was noted between rCBV estimated using two methods (ICC = 0.74, P<0.001). ROC analysis showed that rCBV estimated using T1- and T2*-perfusion methods were able to discriminate between grade-III and grade-IV tumors with AUC of 0.723 and 0.767 respectively. Comparison of AUC values of two ROC curves did not show any significant difference. CONCLUSIONS: In the current study, T1- and T2*-perfusion showed similar diagnostic performance for discrimination of grade III and grade IV gliomas; however, T1-perfusion was found to be better for the evaluation of tumors with intratumoral hemorrhage, postoperative recurrent tumors, and lesions near skull base. We conclude that T1-perfusion MRI with a single dose of contrast could be used as an alternative to T2*-perfusion to overcome the issues associated with this technique in brain tumors for reliable perfusion quantification.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Volume Sanguíneo Cerebral , Glioma/diagnóstico por imagem , Glioma/fisiopatologia , Angiografia por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Angiografia por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Adulto Jovem
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