RESUMO
OBJECTIVE: Kinaesthetic perceptional illusion by visual stimulation (KINVIS) combined with neuromuscular electrical stimulation (NMES) and conventional therapeutic exercise (TherEX) has been shown previously to enhance motor function in stroke patients with chronic hemiparesis. The aim of this preliminary study is to assess the effects of a repetitive KINVIS intervention combined with TherEX, but without NMES, on upper limb motor function of patients with stroke-induced hemiparesis. DESIGN: A quasi-experimental study, with pretest-posttest for 1 group Patients: Ten patients with stroke-induced, chronic, severe upper limb hemiparesis. METHODS: Patients were evaluated before and after a 10-day intervention, during which KINVIS and TherEX were applied for 20 and 60 min, respectively, for 5 days per week (Monday to Friday). Upper limb motor function was assessed using Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT), and resistance to passive movement in flexor muscles was assessed using the Modified Ashworth Scale (MAS). In addition, the amount of use and quality of movement of the affected upper limb in daily life were assessed using Motor Activity Log (MAL). RESULTS: Clinical assessments with FMA, ARAT, MAS, and MAL significantly improved after the intervention period. CONCLUSION: A repetitive KINVIS intervention combined with TherEX may improve upper limb motor function in patients with chronic stroke and severe hemiparesis.
Assuntos
Ilusões , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Paresia , Projetos Piloto , Recuperação de Função Fisiológica , Resultado do Tratamento , Extremidade SuperiorRESUMO
The B-Raf proto-oncogene serine/threonine kinase (B-Raf) is a member of the Raf kinase family. The BRAF V600E mutation occurs frequently in certain brain tumors such as pleomorphic xanthoastrocytoma, ganglioglioma, and pilocytic astrocytoma, and less frequently in epithelioid and giant cell glioblastoma. BRAF V600E mutation in these cases has been canonically detected using Sanger sequencing or immunohistochemistry but not with next-generation sequencing (NGS). Moreover, to our knowledge, there is no detailed report of the BRAF V600E mutation in an adult glioblastoma with classical histologic features (c-GBM). Therefore, we performed NGS analysis to determine the mutational status of BRAF of 13 glioblastomas (GBMs) (11 primary and 2 secondary cases) and detected one tumor harboring the BRAF V600E mutation. We report here the detection of the BRAF V600E mutation in a patient with c-GBM and describe the patient's clinical course as well as the results of histopathological analysis.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Glioblastoma/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Prognóstico , Proto-Oncogene MasRESUMO
Primary central nervous system lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma with a poor prognosis. [18F] 2-fluoro-2-deoxy-D-glucose (FDG) and L-(methyl-11C)-methionine (MET) are the most widely used tracers in oncological positron emission tomography studies for PCNSL and commonly identify hypermetabolic lesions through increased uptake of FDG and MET. However, the mechanisms underlying the uptake of FDG and MET in PCNSL have not been clearly determined. The present study aimed to investigate the mRNA expression levels of glucose transporter (GLUT)1, GLUT3 and L-type amino acid transporter 1 (LAT1) in resected PCNSL specimens, in order to identify whether these transporters are associated with the increased uptake of FDG and MET. A total of 7 patients diagnosed with PCNSL were investigated. The uptake of FDG and MET by the tumors was evaluated based on the maximum standardized uptake value (SUVmax). The quantity of GLUT1, GLUT3 and LAT1 mRNA in the PCNSL specimens was measured to determine whether GLUT1, GLUT3 and/or LAT1 are involved in the increased uptake of FDG and MET in PCNSL. Furthermore, microvessel density (MVD) and cell density (CD) were measured in all the cases. Our results indicated that the expression of GLUT3, but not GLUT1, was significantly correlated with FDG SUVmax and the expression of LAT1 was significantly correlated with MET SUVmax. However, neither MVD nor CD were found to be significantly associated with the uptake of FDG and MET. GLUT3 was identified as a key determinant of FDG accumulation, whereas LAT1 was a key determinant of MET accumulation in PCNSL. Therefore, GLUT3 and LAT1 may represent potential targets for the future development of novel therapeutic agents for PCNSL.
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Reversible lesions on magnetic resonance imaging that transiently restrict diffusion in the splenium of the corpus callosum (SCC) without any other accompanying lesions have been reported in various clinical conditions. We offer the first report of postpartum cerebral angiopathy with reversible SCC lesions.
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Corpo Caloso/patologia , Angiografia por Ressonância Magnética/métodos , Período Pós-Parto , Transtornos Puerperais/patologia , Adulto , Feminino , Humanos , Gravidez , Vasoespasmo IntracranianoRESUMO
Unilateral spatial neglect (USN) is one of the most common symptoms of right hemisphere damage; its classical symptom is that patients fail to respond to information on their left side. It has been postulated that disturbance of 2 separate attentional networks relates to the occurrence of USN. However, little is known about the underlying mechanism and neuronal substrates. In this study, we measured spontaneous neural activity by means of magnetoencephalography in 13 patients with brain damage and 5 control subjects. To study the relationship between functional connectivity at rest and severity of USN symptoms, we determined the imaginary coherence values relating to the inter-hemispherical ventral and dorsal attentional networks, as well as the clinical severity of USN using neuropsychological tests and behavioral rating scales. The present results showed that inter-hemispherical connectivity in the ventral attentional network, especially between the left and right angular gyri, detected in the alpha band is associated with the severity of USN symptoms. This may suggest that connectivity of inter-hemispherical homologous regions of the ventral attentional network in the alpha band could be one of the biomarkers of attentional network imbalance occurring in patients with USN.
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Ritmo alfa/fisiologia , Atenção/fisiologia , Cérebro/fisiopatologia , Rede Nervosa/fisiopatologia , Transtornos da Percepção/fisiopatologia , Descanso/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Transtornos da Percepção/diagnósticoRESUMO
To image cerebral neural activity in ischemic areas, we proposed a novel technique to analyze spontaneous neuromagnetic fields based on standardized low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm). Using a 160-channel whole-head-type magnetoencephalographic system, cerebral magnetic fields were obtained pre- and postoperatively from 5 patients with unilateral internal carotid artery occlusive disease and 16 age-matched healthy volunteers. For quantitative imaging, voxel-based time-averaged intensities of slow waves in 4 frequency bands (0.3-2 Hz, 2-4 Hz, 4-6 Hz and 6-8 Hz) were obtained by the proposed technique based on sLORETA-qm. Positron emission tomography with (15)O gas inhalation ((15)O-PET) was also performed in these patients to evaluate cerebral blood flow and metabolism. In all 5 patients, slow waves in every frequency band were distributed in the area of cerebrovascular insufficiency, as confirmed by (15)O-PET preoperatively. In 4 patients, slow-wave intensities in theta bands (4-6 Hz, 6-8 Hz) decreased postoperatively along with improvements in cerebral blood flow and metabolism, whereas delta bands (0.3-2 Hz, 2-4 Hz) showed no significant differences between pre- and postoperatively. One patient with deterioration of cerebral infarction after surgery showed marked increases in slow-wave intensities in delta bands (0.3-2 Hz, 2-4 Hz) postoperatively, with distribution close to the infarct region. The proposed quantitative imaging of spontaneous neuromagnetic fields enabled clear visualization and alternations of cerebral neural conditions in the ischemic area. This technique may offer a novel, non-invasive method for identifying cerebral ischemia, although further studies in a larger number of patients are warranted.
Assuntos
Isquemia Encefálica/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Disartria/patologia , Eletroencefalografia , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Paresia/patologia , Tomografia por Emissão de PósitronsAssuntos
Mapeamento Encefálico , Estenose das Carótidas , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Magnetoencefalografia/métodos , Masculino , Isótopos de Oxigênio , Tomografia por Emissão de Pósitrons/métodosRESUMO
OBJECTIVE: The objective of this retrospective study is to analyze whether preoperative functional imaging studies using FDG-PET and MEG enable prediction of postoperative seizure outcomes. METHODS: Thirty-six patients with intractable temporal lobe epilepsy were studied. Asymmetry index of tCMRgluc (PET-AI) and the equivalent current dipole intensity of first response of SEF (SEF-AI) were determined preoperatively using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetoencephalography (MEG), respectively. Seizure outcomes were evaluated according to the classification proposed by the International League Against Epilepsy (ILAE) at least 24 months after resection of epileptic focuses. Twelve healthy volunteers were included in this study to determine the normal value. RESULTS: Quantitative analysis revealed mean PET-AI in the patients was 5.4+/-5.2% (significantly different from normal controls); mean SEF-AI was 25.2+/-20.6% (not significantly different). PET-AI was positive (indicative of epileptic focus) in 29 of 36 patients (80.6%), while SEF-AI was positive in 17 of 36 patients (47.2%). Although no significant correlation between PET-AI and SEF-AI was noted (r=0.43), concordant asymmetry in both PET-AI and SEF-AI was significantly associated with better seizure outcome than discordant or paradoxical asymmetry of both factors (p<0.01). CONCLUSIONS: The results suggest that quantitative analysis of tCMRgluc with SEF may be helpful in characterizing the preoperative epileptogenic condition and predicting postoperative seizure outcome in patients with temporal lobe epilepsy, although a constellation of developmental brain abnormalities and environmental factors that together produce epilepsy need to be further explored.
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Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Glucose/metabolismo , Tálamo/metabolismo , Adulto , Criança , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Magnetoencefalografia/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Período Pós-Operatório , Valor Preditivo dos Testes , Estatísticas não Paramétricas , Tálamo/diagnóstico por imagem , Resultado do Tratamento , Adulto JovemRESUMO
PATIENT AND METHODS: Cerebral blood flow and neuromagnetic activity were measured using (123)I-iodoamphetamine-single photon emission computed tomography (IMP-SPECT) and magnetoencephalography (MEG), before and after extracranial-intracranial (EC-IC) bypass surgery in a 55-year-old woman with unilateral middle cerebral artery occlusion that occurred with intraventricular haemorrhage. Frequency analysis of slow waves measured on MEG was performed using an adaptive beam-former method. RESULTS AND DISCUSSION: Distribution of delta waves was observed pre-operatively corresponding to areas of cerebral hypo-perfusion as confirmed by IMP-SPECT but disappeared post-operatively with improvements in cerebral blood flow. Imaging of slow-wave distributions with MEG may represent a new technique for identifying cerebral ischaemia.
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Encéfalo/irrigação sanguínea , Revascularização Cerebral/métodos , Circulação Cerebrovascular/fisiologia , Infarto da Artéria Cerebral Média/cirurgia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/fisiopatologia , Radioisótopos do Iodo , Magnetoencefalografia/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica/fisiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
We investigated the effects of FK228 on cell proliferation and apoptosis against human glioblastoma (GM) T98G, U251MG, and U87MG cells. Upon exposure to FK228, cell proliferation was inhibited, and apoptosis detected by the cleavage of CPP32 was induced. FK228 increased the expression levels of p21 (WAF-1) and of pro-apoptotic Bad protein in all GM cells. Furthermore, FK228 treatment also reduced the anti-apoptotic protein Bcl-xL in all GM cells and anti-apoptotic Bcl-2 in U87MG cells, thereby shifting the cellular equilibrium from life to death. An increased accumulation of histone H4 was detected in the p21 (WAF-1) promoter and the structural gene (exon 2) and the Bad structural gene (exon 2 and 3) upon treatment with FK228, as assessed by chromatin immunoprecipitation (ChIP) assay. Thus, the results indicated that an increased expression of p21 (WAF1) and Bad due to FK228 is regulated, at least in part, by the degree of acetylation of the gene-associated histone. We also found that FK228 inhibits cellular invasiveness and decreases MMP-2 activity. In addition, the growth of transplanted human GM m-3 cells into the subcutaneous tissue of hereditary athymic mice was significantly inhibited, and apoptosis was induced with FK228 treatment. The results suggested that FK228 might be useful in the treatment of human GM, although further studies will be needed.
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Apoptose , Depsipeptídeos , Inibidores de Histona Desacetilases , Peptídeos Cíclicos/farmacologia , Animais , Apoptose/fisiologia , Bromodesoxiuridina , Proteínas de Transporte/metabolismo , Caspase 3 , Caspases/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Transplante de Células/métodos , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , Relação Dose-Resposta a Droga , Éxons/fisiologia , Glioblastoma/patologia , Humanos , Marcação In Situ das Extremidades Cortadas/métodos , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Nus/fisiologia , Regiões Promotoras Genéticas/fisiologia , Proteínas Proto-Oncogênicas , Proteínas Proto-Oncogênicas c-bcl-2 , Fatores de Tempo , Proteína X Associada a bcl-2 , Proteína de Morte Celular Associada a bcl , Proteína bcl-XRESUMO
We investigated the effects of histone deacetylase (HDAC) inhibitors such as sodium butyrate (SB) and trichostatin A (TSA) on the expression of vascular endothelial growth factor (VEGF) by human glioblastoma T98G, U251MG, and U87MG cells. The glioblastoma cells secreted three VEGF isoforms, VEGF (189), (165), and (121), although the expression levels of VEGF differed between the cell types. Treatment with either 5mM SB or 100 ng/ml TSA reduced VEGF secretion in conditioned media and reduced VEGF mRNA expression. We also studied the expression of VEGF-B, -C, and -D mRNA in human glioblastoma cells and their modulation by HDAC inhibitors. The PCR products of VEGF-B (357bp), VEGF-C (501bp), and VEGF-D (484bp) were amplified in all glioblastoma cells examined. Treatment with SB reduced the expression of VEGF-D mRNA in U251MG cells and the expression of VEGF-B mRNA in U87MG cells. TSA treatment reduced the expression of VEGF-D in U251MG cells. These results suggest that HDAC inhibitors reduce VEGF secretion and modulate the expression of the other VEGF family members, and therefore may inhibit angiogenesis in glioblastoma tissues.