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1.
J Neurosci ; 40(7): 1373-1388, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31896671

RESUMO

Microglia exhibit multiple, phenotype-dependent motility patterns often triggered by purinergic stimuli. However, little data exist on motility of human microglia in pathological situations. Here we examine motility of microglia stained with a fluorescent lectin in tissue slices from female and male epileptic patients diagnosed with mesial temporal lobe epilepsy or cortical glioma (peritumoral cortex). Microglial shape varied from ramified to amoeboid cells predominantly in regions of high neuronal loss or closer to a tumor. Live imaging revealed unstimulated or purine-induced microglial motilities, including surveillance movements, membrane ruffling, and process extension or retraction. At different concentrations, ADP triggered opposing motilities. Low doses triggered process extension. It was suppressed by P2Y12 receptor antagonists, which also reduced process length and surveillance movements. Higher purine doses caused process retraction and membrane ruffling, which were blocked by joint application of P2Y1 and P2Y13 receptor antagonists. Purinergic effects on motility were similar for all microglia tested. Both amoeboid and ramified cells from mesial temporal lobe epilepsy or peritumoral cortex tissue expressed P2Y12 receptors. A minority of microglia expressed the adenosine A2A receptor, which has been linked with process withdrawal of rodent cells. Laser-mediated tissue damage let us test the functional significance of these effects. Moderate damage induced microglial process extension, which was blocked by P2Y12 receptor antagonists. Overall, the purine-induced motility of human microglia in epileptic tissue is similar to that of rodent microglia in that the P2Y12 receptor initiates process extension. It differs in that retraction is triggered by joint activation of P2Y1/P2Y13 receptors.SIGNIFICANCE STATEMENT Microglial cells are brain-resident immune cells with multiple functions in healthy or diseased brains. These diverse functions are associated with distinct phenotypes, including different microglial shapes. In the rodent, purinergic signaling is associated with changes in cell shape, such as process extension toward tissue damage. However, there are little data on living human microglia, especially in diseased states. We developed a reliable technique to stain microglia from epileptic and glioma patients to examine responses to purines. Low-intensity purinergic stimuli induced process extension, as in rodents. In contrast, high-intensity stimuli triggered a process withdrawal mediated by both P2Y1 and P2Y13 receptors. P2Y1/P2Y13 receptor activation has not previously been linked to microglial morphological changes.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Glioma/fisiopatologia , Microglia/fisiologia , Receptores Purinérgicos P2Y12/fisiologia , Receptores Purinérgicos P2Y1/fisiologia , Receptores Purinérgicos P2/fisiologia , Neoplasias Supratentoriais/fisiopatologia , Difosfato de Adenosina/farmacologia , Adulto , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Forma Celular/efeitos dos fármacos , Extensões da Superfície Celular/efeitos dos fármacos , Extensões da Superfície Celular/fisiologia , Extensões da Superfície Celular/ultraestrutura , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/patologia , Feminino , Glioma/patologia , Humanos , Microscopia Intravital , Masculino , Microglia/efeitos dos fármacos , Microglia/ultraestrutura , Pessoa de Meia-Idade , Lectinas de Plantas , Agonistas Purinérgicos/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Neoplasias Supratentoriais/patologia , Esclerose Tuberosa/complicações
2.
BMC Anesthesiol ; 20(1): 117, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429839

RESUMO

BACKGROUND: Patients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens. METHODS: This is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer's assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense. DISCUSSION: This randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients' recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population. TRIAL REGISTRATION: The study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177). Principle investigator: Nan Lin (email address: linnan127@gmail.com) and Ruquan Han (email address: hanrq666@aliyun.com) Date of Registration: September 8th, 2016. Country of recruitment: China.


Assuntos
Encéfalo/fisiopatologia , Glioma/cirurgia , Propofol/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Remifentanil/administração & dosagem , Sevoflurano/administração & dosagem , Neoplasias Supratentoriais/cirurgia , Adolescente , Adulto , Idoso , Craniotomia , Feminino , Glioma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Supratentoriais/fisiopatologia , Adulto Jovem
3.
Clin Anat ; 32(4): 524-533, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30702166

RESUMO

Olfactory dysfunction represents a main symptom in olfactory groove meningiomas (OGM). Besides this, olfactory function has been sparsely investigated in patients suffering from supratentorial meningiomas. Here, the authors explore pre- and postoperative variables associated with olfactory dysfunction in supratentorial meningioma patients. This is a retrospective study on supratentorial meningioma patients who underwent meningioma resection between January 2015 and January 2016. Preoperative and postoperative olfactory performance was quantified using a lateralized sniffin' stick odor identification test. Meningiomas affecting the olfactory system (n = 23) were compared to meningiomas in other locations among the control group (n = 40). Meningiomas that affected the olfactory system had odds of 3.6 and 3.7 in being associated with ipsilateral (lesional) and bilateral anosmia, respectively. Subgroup analysis revealed that meningiomas causing a midline shift across the frontal base and older age represented risk factors for preoperative anosmia. The odds of experiencing acquired postoperative ipsilateral anosmia were significantly increased in olfactory system affecting meningiomas (OR 11.1). Subgroup analysis highlighted OGMs to represent the predominant location associated with deterioration. General surgical complications predisposed patients to loss of contralateral (OR 12.3) and bilateral olfactory function (OR 27.8). Older age and meningiomas causing a midline shift across the frontal base predispose patients to preoperative olfactory dysfunction. Resection of OGMs and surgical complications are risk factors for postoperative olfactory deterioration to anosmia. Likely, olfactory dysfunction is underrecognized even in OGMs. In OGM surgery, however, preoperative lateralized testing might be critical to selecting an appropriate surgical route to preserve olfactory function. Clin. Anat. 32:524-533, 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Neoplasias Meníngeas/fisiopatologia , Meningioma/fisiopatologia , Transtornos do Olfato/etiologia , Olfato , Neoplasias Supratentoriais/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Neoplasias Supratentoriais/complicações , Neoplasias Supratentoriais/cirurgia
4.
J Neurooncol ; 138(1): 29-39, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29354850

RESUMO

Ependymomas (EPN) show site specific genetic alterations and a recent DNA methylation profiling study identified nine molecular subgroups. C11orf95-RELA and YAP1 fusions characterise the RELA and YAP1 molecular subgroups, respectively, of supratentorial (ST)-EPNs. Current guidelines recommend molecular subgrouping over histological grade for accurate prognostication. Clinicopathological features of ST-EPNs in correlation with C11orf95-RELA and YAP1 fusions have been assessed in only few studies. We aimed to study these fusions in EPNs, and identify diagnostic and prognostic markers. qRT-PCR and Sanger Sequencing for the detection of C11orf95-RELA, YAP1-MAMLD1 and YAP1-FAM118B fusion transcripts, gene expression analysis for NFKB1, and immunohistochemistry for p53, MIB-1, nestin, VEGF, and L1CAM were performed. 88 EPNs (10-Grade I and 78-Grade II/III) from all sites were included. RELA fusions were unique to Grade II/III ST-EPNs, detected in 81.4% (22/27) and 18.5% (5/27) of pediatric and adult ST-EPNs respectively. ST-EPNs harbouring RELA fusions showed frequent grade III histology (81.5%), clear cell morphology (70.3%), upregulated NFKB1 expression, MIB-1 labelling indices (LI) ≥ 10% (77.8%), and immunopositivity for nestin (95.7%), VEGF (72%), L1CAM (79%), and p53 (64%). Presence of RELA fusions, L1CAM immunopositivity and MIB-1 LI ≥ 10% associated with poor outcome. L1CAM showed 81% concordance with RELA fusions. YAP1-MAMLD1 fusion was identified in a single RELA fusion negative adult anaplastic ST-EPN. RELA fusions are frequent in ST-EPNs and associate with poor outcome. L1CAM is a surrogate immunohistochemical marker. RELA fusion positive ST-EPNs strongly express nestin indicating increased stemness. Further evaluation of the interactions between NFKB and stem cell pathways is warranted.


Assuntos
Ependimoma , NF-kappa B/metabolismo , Nestina/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Supratentoriais , Fator de Transcrição RelA/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ependimoma/metabolismo , Ependimoma/patologia , Ependimoma/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Intervalo Livre de Progressão , Estudos Retrospectivos , Transdução de Sinais/fisiologia , Neoplasias Supratentoriais/metabolismo , Neoplasias Supratentoriais/patologia , Neoplasias Supratentoriais/fisiopatologia , Adulto Jovem
5.
Br J Neurosurg ; 32(6): 619-627, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30260251

RESUMO

Background: A prospective, randomized, double-blind study was designed to assess differences in brain relaxation between 2 doses of 3% HS during elective supratentorial brain tumour surgery.Methods: 60 patients undergoing supratentorial craniotomy for tumour resection were enrolled to receive either 3 mL/kg (group L) or 5 mL/kg (group H) of 3% HS administered at skin incision. Brain relaxation was assessed after dura opening on a scale ranging 1-4 (1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain, 4 = bulging brain). Hemodynamic variables and laboratory values (blood gases, osmolarity, haematocrit, and lactate) were collected before HS infusion and 30, 120 and 360 min after it. Presence of midline shift, postoperative complications, PCU and hospital stay, and mortality after 30 days were also recorded.Results: There was no difference in brain relaxation, with 2.0 (1.0-3.0) and 2.0 (1.0-2.3) (P = 0.535) for patients in groups L and H, respectively. If adjusted for the presence of midline shift, 50% of patients had adequate brain relaxation scores (grades 1 and 2) in group L and 61% in group H (OR 0.64, CI = 0.16-2.49, P = 0.515). No significant differences in perioperative outcome, mortality and length of PCU and hospital stay were observed.Conclusion: 3 mL/kg of 3% HS result in similar brain relaxation scores as 5 mL/kg in patients undergoing craniotomy for supratentorial brain tumour. This study reveals that both high and low doses of 3% HS may be less effective on intraoperative brain relaxation in patients with midline shift.


Assuntos
Craniotomia/métodos , Solução Salina Hipertônica/uso terapêutico , Neoplasias Supratentoriais/cirurgia , Encéfalo/efeitos dos fármacos , Encéfalo/cirurgia , Edema Encefálico/cirurgia , Diuréticos Osmóticos/uso terapêutico , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Manitol/farmacologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Neoplasias Supratentoriais/fisiopatologia
6.
Neuroradiology ; 58(3): 311-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26635295

RESUMO

INTRODUCTION: The need for information regarding functional alterations in patients with brain gliomas is increasing, but little is known about the functional consequences of focal brain tumors throughout the entire brain. Using resting-state functional MR imaging (rs-fMRI), this study assessed functional connectivity in patients with supratentorial brain gliomas with possible alterations in long-distance connectivity and network topology. METHODS: Data from 36 patients with supratentorial brain gliomas and 12 healthy subjects were acquired using rs-fMRI. The functional connectivity matrix (FCM) was created using 32 pairs of cortical seeds on Talairach coordinates in each individual subject. Local and distant connectivity were calculated using z-scores in the individual patient's FCM, and the averaged FCM of patients was compared with that of healthy subjects. Weighted network analysis was performed by calculating local efficiency, global efficiency, clustering coefficient, and small-world topology, and compared between patients and healthy controls. RESULTS: When comparing the averaged FCM of patients with that of healthy controls, the patients showed decreased long-distance, inter-hemispheric connectivity (0.32 ± 0.16 in patients vs. 0. 42 ± 0.15 in healthy controls, p = 0.04). In network analysis, patients showed increased local efficiency (p < 0.05), but global efficiency, clustering coefficient, and small-world topology were relatively preserved compared to healthy subjects. CONCLUSION: Patients with supratentorial brain gliomas showed decreased long-distance connectivity while increased local efficiency and preserved small-world topology. The results of this small case series may provide a better understanding of the alterations of functional connectivity in patients with brain gliomas across the whole brain scale.


Assuntos
Conectoma/métodos , Glioma/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Neoplasias Supratentoriais/fisiopatologia , Adaptação Fisiológica , Adulto , Idoso , Feminino , Glioma/diagnóstico por imagem , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/patologia
7.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-27500773

RESUMO

UNLABELLED: Progress in microneurosurgical techniques, neuroanesthesiology, and intraoperative imaging enables surgery using small incisions and craniotomy, in accordance with the keyhole surgery concept. Supraorbital craniotomy is the most widespread minimally invasive approach. There are a number of supraorbital craniotomy modifications, regarding different soft tissue incisions and the extent of craniotomy. We present the first results of using mini-orbitozygomatic craniotomy for aneurysms of the anterior circle of Willis and space-occupying lesions of the anterior and middle cranial fossae performed through an eyebrow incision. MATERIAL AND METHODS: Forty five patients were operated on using mini-orbitozygomatic (MOZ) craniotomy in the period between March 2014 and December 2015. Fifteen supratentorial aneurysms were clipped, and 30 space-occupying lesions were resected. Most patients had unruptured aneurysms (10 patients). Five patients had a history of SAH. The aneurysm localization was as follows: 8 anterior communicating artery aneurysms, 4 aneurysms of the internal carotid artery in the area of the posterior communicating artery orifice, and 3 ophthalmic aneurysms. The Hunt-Hess scale was used to evaluate the patients' condition, and the Fisher scale was used to quantify SAH volume. Surgery was performed 14 days after SAH, on average. Contrast-enhanced MRI of the brain was the diagnostic method of choice in a group of patients with space-occupying lesions within the anterior and middle cranial fossae. In some cases, patients underwent CT with reconstruction for assessment of the skull base bone structures. The mean age of patients was 58.3 years. RESULTS: All aneurysms were completely excluded from the cerebral blood flow. No serious complications and deaths in a group of aneurysm patients occurred. Complete tumor removal was performed in 28 patients. Two patients having pituitary macroadenomas with supra- and parasellar spread underwent subtotal resection due to adenoma invasion into the cavernous sinus. Mortality in this group was 3.3% (1 patient). Postoperative complications were evaluated after 2 weeks and 6 months. The postoperative cosmetic result after 3 and 6 months after surgery was assessed by patients as excellent. CONCLUSION: Mini-orbitozygomatic craniotomy is an alternative to classic approaches and can be assistive in surgery for skull base aneurysms and tumors. Selection of candidates for this keyhole surgery should be based on their critical assessment.


Assuntos
Fossa Craniana Média/cirurgia , Craniotomia/métodos , Aneurisma Intracraniano/cirurgia , Neoplasias Supratentoriais/cirurgia , Adulto , Idoso , Circulação Cerebrovascular , Fossa Craniana Média/fisiopatologia , Feminino , Humanos , Aneurisma Intracraniano/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Supratentoriais/fisiopatologia
8.
Anesteziol Reanimatol ; 61(2): 143-6, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27468507

RESUMO

In some cases after elective neurosurgical procedures we use technique of delayed awakening of patients. Prolonged sedation however can hide the development of epileptic seizures and lead to the status epilepticus formation. This article is a demonstration and discussion of a clinical case of nonconvulsive status epilepticus during delayed awakening of the patient due to prolonged sedation after elective neurosurgical interventionsforsupratentorial brain tumor Presented case suggests the presence of significant risk of nonconvulsive status epilepticus during prolonged sedation. For early detection we advise to use continuous EEG monitoring during the entire period of sedation.


Assuntos
Recuperação Demorada da Anestesia/fisiopatologia , Procedimentos Neurocirúrgicos/efeitos adversos , Estado Epiléptico/fisiopatologia , Neoplasias Supratentoriais/cirurgia , Recuperação Demorada da Anestesia/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Monitorização Fisiológica , Estado Epiléptico/etiologia , Neoplasias Supratentoriais/complicações , Neoplasias Supratentoriais/fisiopatologia
9.
Acta Anaesthesiol Scand ; 57(10): 1301-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24032397

RESUMO

BACKGROUND: Few studies look into cerebral blood flow (CBF) changes during emergence from general anaesthesia for craniotomy. The purpose of this study was to assess CBF changes during emergence from general anaesthesia for craniotomy, through monitoring blood oxygen saturation of jugular vein bulb (SjvO2 ) and transcranial Doppler (TCD). METHODS: We enrolled 30 patients undergoing selective craniotomy (group C) for supratentorial brain tumour resection and 30 patients undergoing selective abdominal surgery (group A). Mean velocity of middle cerebral artery (Vmca), mean arterial pressure (MAP), SjvO2 (only measured in group C), and arterial CO2 partial pressure were measured before anaesthesia, at tracheal extubation, and 30, 60, 90, 120 min after extubation. RESULTS: Vmca of the same side of tumour was significantly higher than contralateral Vmca before anaesthesia and at all times after extubation in group C. The ipsilateral Vmca increased significantly (95.7 ± 16.9 cm/s vs. 63.7 ± 6.7 cm/s, P < 0.01) at extubation in group C, then declined but still above baseline significantly in the first 2 h after extubation. While Vmca of the right side changed only slightly (63.6 ± 7.7 cm/s vs. 61.8 ± 8.1 cm/s, P < 0.01) but significantly at extubation in group A. SjvO2 increased significantly (81.4% ± 7.4% vs. 60.9% ± 3.7%, P < 0.01) at extubation in group C, and remained above baseline significantly for 2 h. There was no significant correlation between Vmca and MAP at any time. CONCLUSIONS: Cerebral hyperaemia occurs after supratentorial brain tumour resection surgery. The hyperaemia is more pronounced on the same side as the tumour.


Assuntos
Anestesia por Inalação/métodos , Circulação Cerebrovascular/efeitos dos fármacos , Craniotomia/métodos , Hiperemia/etiologia , Isoflurano/farmacologia , Neoplasias Supratentoriais/cirurgia , Adulto , Pressão Arterial/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Prospectivos , Neoplasias Supratentoriais/fisiopatologia
10.
Patol Fiziol Eksp Ter ; (3): 47-50, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24340619

RESUMO

Using the Doppler ultrasonography method the condition of brain blood circulation of 90 patients with supratentorial brain tumors (gliomas--43, meningiomas--34, metastasis--9) during pre-surgical period was studied. The factors changing brain blood circulation at patients with with supratentorial brain tumors were brain displacement, increase of intracranial pressure, histologic structure and the first symptoms duration of illness. Localization (for an exception of an occipital lobe) and the size of a tumor directly didn't render influence on blood circulation parameters.


Assuntos
Córtex Cerebral/irrigação sanguínea , Glioma/fisiopatologia , Neoplasias Supratentoriais/fisiopatologia , Adulto , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Feminino , Glioma/diagnóstico por imagem , Humanos , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/fisiopatologia , Neoplasias Supratentoriais/diagnóstico por imagem , Ultrassonografia
11.
Acta Neuropathol ; 123(5): 711-25, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22109108

RESUMO

Epigenetic alterations, including methylation, have been shown to be an important mechanism of gene silencing in cancer. Ependymoma has been well characterized at the DNA copy number and mRNA expression levels. However little is known about DNA methylation changes. To gain a more global view of the methylation profile of ependymoma we conducted an array-based analysis. Our data demonstrated tumors to segregate according to their location in the CNS, which was associated with a difference in the global level of methylation. Supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors, similar to the 'CpG island methylator phenotype' (CIMP) identified in glioma and colon carcinoma. This hypermethylated profile was associated with an increase in expression of genes encoding for proteins involved in methylating DNA, suggesting an underlying mechanism. An integrated analysis of methylation and mRNA expression array data allowed us to identify methylation-induced expression changes. Most notably genes involved in the control of cell growth and death and the immune system were identified, including members of the JNK pathway and PPARG. In conclusion, we have generated a global view of the methylation profile of ependymoma. The data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal, but not posterior fossa ependymomas. Hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis.


Assuntos
Ependimoma/genética , Ependimoma/fisiopatologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Genes Supressores de Tumor/fisiologia , Neoplasias da Coluna Vertebral/fisiopatologia , Neoplasias Supratentoriais/fisiopatologia , Apoptose/fisiologia , Proliferação de Células , Criança , Análise por Conglomerados , Estudos de Coortes , Metilação de DNA/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Transdução de Sinais/genética , Neoplasias da Coluna Vertebral/genética , Estatística como Assunto , Neoplasias Supratentoriais/genética
12.
Middle East J Anaesthesiol ; 21(1): 23-33, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21991729

RESUMO

BACKGROUND: Preliminary data on the perioperative use of dexmedetomidine in patients undergoing craniotomy for brain tumor under general anesthesia indicate that the intraoperative administration of dexmedetomidine is opioid-sparing, results in less need for antihypertensive medication, and may offer greater hemodynamic stability at incision and emergence. Dexmedetomidine, alpha 2 adrenoceptor agonist, is used as adjuvant to anesthetic agents. Relatively recent studies have shown that dexmedetomidine is able to decrease circulating plasma norepinephrine and epinephrine concentration in approximately 50%, decreases brain blood flow by directly acting on post-synaptic alpha 2 receptors, decreases CSF pressure without ischemic suffering and effectively decreases brain metabolism and intracranial pressure and also, able to decrease injury caused by focal ischemia. PURPOSE: This prospective, randomized, double-blind study was designed to assess the perioperative effect of intraoperative infusion of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anesthesia. METHODS: Fourty patients with CT- scanning proof of supratentorial tumors were classified equally into 2 groups (twenty patients in each group). Group A:--Dexmedetomidine was given as a bolus dose of 1 microg/kg in 20 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4 microg/kg/hr. The infusion was discontinued when surgery ended. Group B:--The patients received similar volumes of saline. RESULTS: Heart rate and mean arterial blood pressure, decreased significantly in patients of group A (dexmedetomidine group) compared to group B (placebo group) (p-value < 0.05). There was no significant statistical difference between the two groups regarding the central venous pressure and arterial partial pressure of carbon dioxide (p-value > 0.05). The intraoperative end-tidal sevoflurane (%) in patients of group A was less than in patients of group B (p-value < 0.05). The intracranial pressure decreased in patients of Group A more than group B (p-value < 0.05). The Glasgow coma scale (GCS) improved in patients of group A and deteriorated in patients of Group B with significant statistical difference between the two groups (p-value < 0.05). The total fentanyl requirements from induction to extubation of patients increased in patients of group B more than in patients of group A (p-value < 0.05). The total postoperative patients' requirements for antiemetic drugs within the 2 hours after extubation decreased in patients of group A more than group B (p-value < 0.05). The postoperative duration from the end of surgery to extubation decreased significantly in patients of group A more than group B (p-value < 0.05). The total urine output during the duration from drug administration to extubation of patients increased in patients of group A more than group B (p-value < 0.05). CONCLUSION: Continuous intraoperative infusion of dexmedetomidine during craniotomy for supratentorial tumors under general anesthesia maintained the hemodynamic stability, reduced sevoflurane and fentanyl requirements, decreased intracranial pressure, and improved significantly the outcomes.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Anestesia Geral , Craniotomia , Dexmedetomidina/uso terapêutico , Neoplasias Supratentoriais/cirurgia , Adulto , Idoso , Pressão Sanguínea , Método Duplo-Cego , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Supratentoriais/fisiopatologia
13.
Neuropathol Appl Neurobiol ; 36(5): 399-410, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20202125

RESUMO

AIMS: Studying the molecules and signalling pathways regulating glioma invasiveness is a major challenge because these processes determine malignancy, progression, relapse and prognosis. We took advantage of our previous study focused on genes that were critical in tumour invasion to further study here an unknown sequence, referred to as KIAA0510, the chromosomal location of which was 1q25, described as a 5596-bp long mRNA and that we found to be significantly overexpressed in pilocytic astrocytomas compared with glioblastomas. METHODS AND RESULTS: Using in silico analysis as well as Polymerase chain reaction techniques, we decipher the full genomic characterization of the KIAA0510 sequence and demonstrate that KIAA0510 constitutes the 3'-untranslated region of tenascin-R gene. We have clearly confirmed the overexpression of tenascin-R in pilocytic astrocytomas vs. glioblastomas at mRNA and protein levels. We also analysed a large series of various brain tumours and found that in the group of astrocytic tumours, tenascin-R expression decreased with malignancy, whereas oligodendrogliomas sometimes retained a high level of tenascin-R even in high-grade tumours. Gangliogliomas strongly expressed tenascin-R too. In contrast, ependymomas and meningiomas were negative. In normal brain, tenascin-R was exclusively expressed by normal oligodendrocytes and subsets of neurones during post-natal development and in adulthood, where it could differentially affect cellular adhesiveness and/or differentiation. CONCLUSION: KIAA0510, the 3'-untranslated region of the tenascin-R gene, and tenascin-R are overexpressed in pilocytic astrocytomas. Gangliogliomas shared with pilocytic astrocytomas strong tenascin-R expression. Whether tenascin-R overexpression negatively influences brain invasion remains to be determined.


Assuntos
Astrocitoma/genética , Neoplasias Cerebelares/genética , Regulação Neoplásica da Expressão Gênica , Tenascina/genética , Regiões 3' não Traduzidas/genética , Adolescente , Adulto , Idoso , Astrocitoma/fisiopatologia , Neoplasias Cerebelares/fisiopatologia , Criança , Pré-Escolar , Ependimoma/genética , Ependimoma/fisiopatologia , Ganglioglioma/genética , Ganglioglioma/fisiopatologia , Humanos , Lactente , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/fisiopatologia , Meningioma/genética , Meningioma/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Supratentoriais/genética , Neoplasias Supratentoriais/fisiopatologia , Adulto Jovem
14.
Anesth Analg ; 110(3): 903-7, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-20185666

RESUMO

BACKGROUND: In this study, we compared the effects of 3% hypertonic saline (HTS) and 20% mannitol on brain relaxation during supratentorial brain tumor surgery, intensive care unit (ICU) stays, and hospital days. METHODS: This prospective, randomized, and double-blind study included patients who were selected for elective craniotomy for supratentorial brain tumors. Patients received either 160 mL of 3% HTS (HTS group, n = 122) or 150 mL of 20% mannitol infusion (M group, n = 116) for 5 minutes at the start of scalp incision. The PCO(2) in arterial blood was maintained within 35 to 40 mm Hg, arterial blood pressure was controlled within baseline values +/-20%, and positive fluid balance was maintained intraoperatively at a rate of 2 mL/kg/h. Outcome measures included fluid input, urine output, arterial blood gases, serum sodium concentration, ICU stays, and hospital days. Surgeons assessed the condition of the brain as "tight," "adequate," or "soft" immediately after opening the dura. RESULTS: Brain relaxation conditions in the HTS group (soft/adequate/tight, n = 58/43/21) were better than those observed in the M group (soft/adequate/tight, n = 39/42/35; P = 0.02). The levels of serum sodium were higher in the HTS group compared with the M group over time (P < 0.001). The average urine output in the M group (707 mL) was higher than it was in the HTS group (596 mL) (P < 0.001). There were no significant differences in fluid input, ICU stays, and hospital days between the 2 groups. CONCLUSIONS: Our results suggest that HTS provided better brain relaxation than did mannitol during elective supratentorial brain tumor surgery, whereas it did not affect ICU stays or hospital days.


Assuntos
Craniotomia , Pressão Intracraniana/efeitos dos fármacos , Manitol/administração & dosagem , Solução Salina Hipertônica/administração & dosagem , Neoplasias Supratentoriais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Diurese/efeitos dos fármacos , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Infusões Intravenosas , Longevidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sódio/sangue , Soluções , Neoplasias Supratentoriais/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
World Neurosurg ; 138: e66-e71, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32014546

RESUMO

OBJECTIVE: Measuring functional connectivity (FC) and resting state networks (RSNs) using resting state functional magnetic resonance imaging is a method of preoperative planning in patients with brain tumors. However, the baseline FC and RSNs are altered in patients with brain tumors. In this study, we examined changes in inter-network FC in patients with brain tumors. METHODS: We performed region of interest (ROI) analysis of FC in 34 patients with supratentorial gliomas and 14 healthy subjects. We performed bivariate correlation analyses at the level of each subject. Resulting correlations were Fischer Z-transformed. The used nodes included 132 ROIs from the automated anatomical labeling atlas in addition to 32 ROIs representing the different functional brain networks. We investigated second-level effects by contrasting dummy encoded covariates representing the effects of group membership on functional connectivity. The significant 2-sided P value with corrected false discovery rate was set to 0.05. We set the t contrast between the group of patients with brain tumors and the group of healthy subjects to detect the effects of tumors on inter-network connectivity. RESULTS: Overall, the inter-network FC was significantly higher in patients with brain tumors compared with healthy subjects. The anterior and posterior cerebellar networks, as well as the supratentorial network, showed significantly higher connectivity in patients with brain tumors than in healthy subjects. CONCLUSION: Although brain tumors affect the FC and RSNs, the current study showed higher baseline inter-network connectivity in patients with brain tumors, which could indicate an intrinsic neural compensatory mechanism.


Assuntos
Glioma/fisiopatologia , Vias Neurais/fisiopatologia , Neoplasias Supratentoriais/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Descanso , Estudos Retrospectivos , Neoplasias Supratentoriais/diagnóstico por imagem , Adulto Jovem
17.
World Neurosurg ; 142: e10-e17, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32360673

RESUMO

OBJECTIVE: In this study we present the nature and characteristic of the fluctuation of blood oxygen level-dependent (BOLD) signals measured from brain tumors. METHODS: Supratentorial astrocytomas, which were neither operated nor previously managed with chemotherapy or radiotherapy, were segmented, and the time series of the BOLD signal fluctuations were extracted. The mean (across patients) power spectra were plotted for the different World Health Organization tumor grades. One-way analysis of variance (ANOVA) was performed to identify significant differences between the power spectra of different tumor grades. Results were considered significant at P < 0.05. RESULTS: A total of 58 patients were included in the study. This group of patients included 1 patient with grade I glioma; 15 with grade II; 12 with grade III; and 30 with grade IV. The power spectra of the tumor time series were individually inspected, and all tumors exhibited high peaks at the lower frequency signals, but these were more pronounced in high-grade tumors. ANOVA showed a significant difference in power spectra between groups (P = 0.000). Post hoc analysis with Bonferroni correction showed a significant difference between grade II and grade III (P = 0.012) and grade IV (P = 0.000). There was no significant power spectra difference between grade III and IV tumors (P = 1). CONCLUSIONS: The power spectra of BOLD signals from tumor tissue showed fluctuations in the low-frequency signals and were significantly correlated with tumor grade. These signals could have a misleading effect when analyzing resting state functional magnetic resonance imaging and could be also viewed as a potential method of tumor characterization.


Assuntos
Astrocitoma/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Supratentoriais/diagnóstico por imagem , Adulto , Idoso , Astrocitoma/patologia , Astrocitoma/fisiopatologia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Neuroimagem Funcional , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Glioblastoma/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Acoplamento Neurovascular , Neoplasias Supratentoriais/patologia , Neoplasias Supratentoriais/fisiopatologia
18.
Childs Nerv Syst ; 25(3): 367-71, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18972117

RESUMO

INTRODUCTION: The clinical manifestations of obstructive hydrocephalus vary with the age of the patient, duration of the condition, and etiology of the hydrocephalus. CASE REPORT: A 14-year-old boy presented with diurnally fluctuating dysarthria, dysequilibrium of the gait, and retropulsion, probably due to transient obstruction by a tumor at the entrance of the cerebral aqueduct of the pineal region. This fluctuation was ascertained clinically by assessing the ICARS score 5 h after the patient was in the supine and erect positions. CONCLUSION: This result suggests that the symptoms of hydrocephalus are possibly associated with a check-valve mechanism of the pineal tumor and may be related to transient compression of the basal ganglia and frontal lobes.


Assuntos
Astrocitoma/complicações , Hidrocefalia/etiologia , Hidrocefalia/fisiopatologia , Glândula Pineal/patologia , Pinealoma/complicações , Neoplasias Supratentoriais/complicações , Adolescente , Astrocitoma/patologia , Astrocitoma/fisiopatologia , Líquido Cefalorraquidiano , Humanos , Imageamento por Ressonância Magnética , Masculino , Pinealoma/patologia , Pinealoma/fisiopatologia , Neoplasias Supratentoriais/patologia , Neoplasias Supratentoriais/fisiopatologia
19.
World Neurosurg ; 128: e165-e176, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30995557

RESUMO

OBJECTIVE: In this study, we present our experience using resting-state functional magnetic resonance imaging (rs-fMRI) in preoperative planning. We performed group analysis to demonstrate the effects of brain tumor on resting-state networks (RSNs). METHODS: Thirty patients with supratentorial gliomas were included in the study. Preoperative rs-fMRI and structural magnetic resonance imaging were performed in all cases. The rs-fMRI was preprocessed (realignment, slice time correction, coregistration to structural images, normalization, and smoothing). The structural images were segmented and normalized. Band filtering and denoising were applied to the functional images. Connectivity analysis was performed using seed-based connectivity analysis (SCA) at single subject level and group level. Correlation algorism has been used with r > 0.5. RESULTS: RSNs could be detected in all patients. They showed similarity to the results of the task-based fMRI, when task-based fMRI was feasible. Detection of the networks was also possible in patients with neurologic deficits, in whom task-based fMRI was not possible. We could use SCA in patients under anesthesia. High-level networks (default mode, salience, and dorsal attention networks) were detectable but showed a wide spectrum of spatial alterations and component disconnections. CONCLUSIONS: rs-fMRI is a feasible method for extended brain mapping. Diverse RSNs could be detected in patients with brain tumors and could be applied in preoperative planning. SCA was a robust and direct approach for data analysis and could answer specific clinically relevant questions. However, further studies are needed to validate the technique and its clinical impact.


Assuntos
Glioma/diagnóstico por imagem , Glioma/cirurgia , Vias Neurais/diagnóstico por imagem , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/cirurgia , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Estudos de Viabilidade , Feminino , Neuroimagem Funcional , Glioma/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Cuidados Pré-Operatórios , Descanso , Neoplasias Supratentoriais/fisiopatologia , Adulto Jovem
20.
World Neurosurg ; 123: e549-e556, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30528526

RESUMO

OBJECTIVE: We investigated seizure outcomes of patients with supratentorial meningiomas (ST-MNGs) treated with stereotactic radiosurgery (SRS). METHODS: One hundred and thirty-three patients with a total of 144 ST-MNGs, who were treated with SRS between 2009 and 2016, were included in this study. The mean age was 59.0 ± 11.9 years (range, 13-87 years). The mean follow-up duration was 49.8 ± 24.5 months (range, 9-96 months). The median tumor volume was 2.60 cm3 (range, 0.06-32.40 cm3), and the median marginal dose was 14.0 Gy (range, 11.0-20.0 Gy). Postradiosurgery peritumoral edema (PRPTE) was developed in 43 lesions (29.9%). RESULTS: New seizure attacks developed in 16 patients (12.0%) after SRS (first seizure attack in 14 [87.5%]; seizure aggravation in 2 [12.5%]). In 15 patients with new seizure attacks (93.8%), PRPTE was proved on magnetic resonance imaging. The mean interval between SRS and new seizure attack was 6.6 ± 7.1 (range, 0.23-28.8) months. Simple partial seizure was the most common type of seizure (n = 9 [56.3%]). Five patients (31.3%) were seizure-free with antiepileptic drug (AED) medication (3 [18.8%] withdrew AEDs during the follow-up period); however, the remaining 11 patients (68.7%) did not achieve seizure-free outcomes even with AED medication. Moreover, seizures became intractable in 8 patients (50.0%). From multivariate analysis, the significant predictors of post-SRS seizure attack were PRPTE (odds ratio, 53.99; 95% confidence interval, 5.214-559.1; P = 0.001) and brain-tumor contact-surface index (odds ratio, 2.466; 95% confidence interval, 1.183-5.138; P = 0.016). CONCLUSIONS: The clinical outcomes of seizures after SRS for ST-MNGs fall short of our expectation, and seizures seem to be uncontrollable and even intractable.


Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radiocirurgia , Convulsões/etiologia , Neoplasias Supratentoriais/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/fisiopatologia , Meningioma/diagnóstico por imagem , Meningioma/fisiopatologia , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/fisiopatologia , Carga Tumoral , Adulto Jovem
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