RESUMO
Although conventional proton magnetic resonance imaging has increased our ability to detect brain tumors, it has not enhanced to nearly the same degree our ability to diagnose tumor type. Proton magnetic resonance spectroscopy is a safe, noninvasive means of performing biochemical analysis in vivo. Using this technique, we characterized and classified tissue from normal brains, as well as tissue from the five most common types of adult supratentorial brain tumors. These six tissue types differed in their pattern across the six metabolites measured. 'Leaving-one-out' linear discriminant analyses based on these resonance profiles correctly classified 104 of 105 spectra, and, whereas conventional preoperative clinical diagnosis misclassified 20 of 91 tumors, the linear discriminant analysis approach missed only 1. Thus, we have found that a pattern-recognition analysis of the biochemical information obtained from proton magnetic resonance spectroscopy can enable accurate, noninvasive diagnosis of the most prevalent types of supratentorial brain tumors.
Assuntos
Neoplasias Encefálicas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Alanina/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Biomarcadores , Encéfalo/metabolismo , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/metabolismo , Colina/metabolismo , Creatina/metabolismo , Diagnóstico Diferencial , Humanos , Lactatos/metabolismo , Ácido Láctico , Metabolismo dos Lipídeos , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/metabolismo , Meningioma/diagnóstico , Meningioma/metabolismo , Neoplasias Supratentoriais/classificação , Neoplasias Supratentoriais/diagnóstico , Neoplasias Supratentoriais/metabolismoRESUMO
In this article, we review recently published data on the role of the insula in refractory partial epilepsy and summarize our own experience in the investigation and treatment of this entity. Case studies and evoked responses obtained from insular cortical stimulation reveal a wide array of clinical manifestations which may mimic temporal, frontal or parietal lobe seizures. Clinicians should hence lower their threshold to sample the insula with intracerebral electrodes. Lack of recognition of insular seizures may explain part of epilepsy surgery failures. Advances in microneurosurgery open the way to safer insular resection.
Assuntos
Epilepsia do Lobo Temporal/diagnóstico , Eletroencefalografia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Humanos , Imageamento por Ressonância Magnética , Procedimentos Neurocirúrgicos , QuebequeRESUMO
OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (1 month after surgery), lost benefit (delayed failure, DF). RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF.
Assuntos
Eletrodos Implantados/efeitos adversos , Microeletrodos/efeitos adversos , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Atividades Cotidianas , Idoso , Antiparkinsonianos/uso terapêutico , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Transtornos Neurológicos da Marcha/complicações , Humanos , Hipocinesia/complicações , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia , Técnicas Estereotáxicas , Falha de TratamentoRESUMO
BACKGROUND: Until recently, neurosurgeons eagerly removed cerebellar lesions without consideration of future cognitive impairment that might be caused by the resection. In children, transient cerebellar mutism after resection has lead to a diminished use of midline approaches and vermis transection, as well as reduced retraction of the cerebellar hemispheres. The role of the cerebellum in higher cognitive functions beyond coordination and motor control has recently attracted significant interest in the scientific community, and might change the neurosurgical approach to these lesions. The aim of this study was to investigate the specific effects of cerebellar lesions on memory, and to assess a possible lateralisation effect. METHODS: We studied 16 patients diagnosed with a cerebellar lesion, from January 1997 to April 2005, in the "Centre Hospitalier Universitaire Vaudois (CHUV)", Lausanne, Switzerland. Different neuropsychological tests assessing short term and anterograde memory, verbal and visuo-spatial modalities were performed pre-operatively. RESULTS: Severe memory deficits in at least one modality were identified in a majority (81%) of patients with cerebellar lesions. Only 1 patient (6%) had no memory deficit. In our series lateralisation of the lesion did not lead to a significant difference in verbal or visuo-spatial memory deficits. FINDINGS: These findings are consistent with findings in the literature concerning memory deficits in isolated cerebellar lesions. These can be explained by anatomical pathways. However, the cross-lateralisation theory cannot be demonstrated in our series. The high percentage of patients with a cerebellar lesion who demonstrate memory deficits should lead us to assess memory in all patients with cerebellar lesions.
Assuntos
Amnésia/fisiopatologia , Neoplasias Cerebelares/fisiopatologia , Dominância Cerebral/fisiologia , Adolescente , Adulto , Idoso , Amnésia/diagnóstico , Amnésia Anterógrada/diagnóstico , Amnésia Anterógrada/fisiopatologia , Astrocitoma/diagnóstico , Astrocitoma/fisiopatologia , Astrocitoma/cirurgia , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/secundário , Neoplasias Cerebelares/cirurgia , Cerebelo/fisiopatologia , Cerebelo/cirurgia , Feminino , Seguimentos , Glioblastoma/diagnóstico , Glioblastoma/fisiopatologia , Glioblastoma/cirurgia , Hemangioblastoma/diagnóstico , Hemangioblastoma/fisiopatologia , Hemangioblastoma/cirurgia , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/fisiopatologia , Hemangioma Cavernoso/cirurgia , Humanos , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/fisiopatologia , Meduloblastoma/cirurgia , Memória de Curto Prazo/fisiologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/fisiopatologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/fisiopatologia , Meningioma/cirurgia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Aprendizagem Verbal/fisiologiaRESUMO
Electrical stimulation of deep brain structures is a promising new technology for the treatment of medically intractable seizures. Performed in vitro and on animal models of epilepsy, electrical stimulation has shown to reduce seizure frequency. Preliminary results on humans are encouraging. However, such improvements emerge despite a lack of understanding of the precise mechanisms underlying electrical stimulation either delivered directly on the epileptogenic zone (direct control) or through an anatomical relay of cortico-subcortical networks (remote control). Anatomical targets such as the thalamus (centromedian nucleus, anterior thalamus, mamillary body and mamillothalamic tracts), the subthalamic nucleus, the caudate nucleus and direct stimulation of the hippocampal formation have been successfully investigated. Although randomized controlled studies are still missing, deep brain stimulation is a promising treatment option for a subgroup of carefully selected patients with intractable epilepsy who are not candidates for resective surgery. The effectiveness, the optimal anatomic targets, the ideal stimulation parameters and devices, as well as patient selection criteria are still to be defined.
Assuntos
Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/métodos , Epilepsia/patologia , Epilepsia/terapia , Vias Neurais/fisiopatologia , Animais , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/patologiaRESUMO
INTRODUCTION: Radiosurgery is presently becoming an alternative to microsurgical resection of acoustic neuromas. The interest of radiosurgery consists in its lower morbidity compared to surgery and likely in similar rates of long-term tumor control. The goal of our study was to assess the clinical outcome (hearing preservation and neurological complications) as well as tumor control after low-dose radiosurgery for unilateral acoustic neuromas. MATERIAL AND METHODS: Since April 2002, 22 patients with untreated acoustic neuromas underwent stereotactic radiosurgery using a linear accelerator (LINAC) and a micromultileaf collimator (mMLC, Brain Lab) at a low-dose of 12 Gy. The average age was 56.4 years (range 29-73 years). The treatment volume was 0.03 to 6.04 cm(3) (median 1.85 cm(3)). The median follow-up period was 18 months (range 6-36 months). RESULTS: No morbidity was observed during the treatment. Preservation of a serviceable hearing (classes I and II according to the Gardner-Robertson scale) was achieved in 10 of 14 patients (71%). Radiological tumor growth control was obtained in all patients (100%). Trigeminal neuropathy was observed in two patients. One of these patients also experienced a slight facial weakness. CONCLUSIONS: Low dose radiosurgery provides a low rate of post-therapeutic morbidity and yields the preservation of a serviceable hearing in 70% of cases. Tumor control is observed in all patients, but a longer follow-up period is needed to confirm the stability of the tumor size.
Assuntos
Neuroma Acústico/cirurgia , Radiocirurgia/instrumentação , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neuroma Acústico/patologia , Resultado do TratamentoRESUMO
Rasmussen encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patients.
Assuntos
Encefalite/diagnóstico , Encefalite/terapia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Autoimunidade , Citotoxicidade Imunológica , Diagnóstico Diferencial , Encefalite/etiologia , Encefalite/imunologia , Epilepsia/etiologia , Humanos , Imunoterapia/métodos , Linfócitos T Citotóxicos/imunologiaRESUMO
We have studied the effects of insulin, epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor, and steroid hormones (estradiol, progesterone, and cortisol) on human meningioma cell proliferation and DNA synthesis in a serum-free culture system. The growth factors, particularly EGF and FGF, increased DNA synthesis in a dose-dependent manner as measured by [3H]thymidine incorporation, and they stimulated submaximal cell proliferation. No individual factor or combination of factors was able to successfully reproduce the effects of 10% fetal calf serum (FCS) on cell growth, although a combination of platelet-derived growth factor (5 units/ml) and EGF (10 ng/ml) synergistically stimulated DNA synthesis to near maximal levels. In addition, serum dependency was observed in studies involving the mitogenic effects of insulin, EGF, or FGF. Both EGF and FGF (10 ng/ml) maximally stimulated cell growth in the presence of 5% FCS. The effects of steroid hormones on cell proliferation, individually or in combination with growth factors or charcoal-treated FCS, were also evaluated. Estradiol (100 nM) significantly increased cell number over control values only in the presence of charcoal-treated FCS; no effects of progesterone or cortisol on cell proliferation were observed. In conclusion, both EGF and FGF stimulated cell proliferation and DNA synthesis in human meningioma cultures in a serum-free system, whereas steroid hormones were without effect. It appears that additional serum components are required for both estradiol-stimulated growth and for maximal proliferation of human meningioma cells under serum-free conditions.
Assuntos
DNA de Neoplasias/biossíntese , Meningioma/patologia , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/ultraestrutura , Ciclo Celular/efeitos dos fármacos , Meios de Cultura , Sinergismo Farmacológico , Substâncias de Crescimento/farmacologia , Humanos , Meningioma/ultraestrutura , Pessoa de Meia-Idade , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/ultraestrutura , Esteroides/farmacologiaRESUMO
Studies have indicated that two transcriptionally active units can repress one another when they lie adjacent in head-to-tail tandem on a chromosome. Repression of a downstream (3') unit by an upstream (5') unit is known as "transcriptional interference", whereas repression of a 5' unit by a 3' unit is termed "promoter suppression". These two processes can occur between head-to-tail tandem copies of a transgene, or between transgenes and adjacent chromosomal genes. Interference can be blocked by inserting a transcription terminator between adjacent units. Here, we report that "promoter suppression" could be blocked by the insulator 5' DNaseI hypersensitive site 4, or matrix/scaffold attachment regions (MAR/SARs), when these elements were interposed between adjacent units. Because intergenic spacers of many repeated eukaryotic genes contain MAR/SARs and insulators, our observations suggest that these elements have the ability to segregate repeated genes into domains that act independently of one another. Our observations also suggest strategies to design transgenes that can act as autonomous units of expression.
Assuntos
Galinhas/genética , Cromatina/genética , Inativação Gênica , Globinas/genética , Regiões Promotoras Genéticas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Animais , Sítios de Ligação , Linhagem Celular , Cromatina/química , Cromatina/metabolismo , DNA/genética , DNA/metabolismo , Genes Reporter/genética , Genes Virais/genética , Inibidores de Histona Desacetilases , Histona Desacetilases/metabolismo , Camundongos , Modelos Genéticos , Simplexvirus/genética , Regiões Terminadoras Genéticas/genética , Timidina Quinase/genética , Transcrição Gênica/genética , TransfecçãoRESUMO
OBJECTIVE: Lesch-Nyhan syndrome is a rare and debilitating condition characterized by dystonia and self-mutilating behavior. In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS). METHODS: Microrecordings were performed on 162 neurons along four tracks aimed at the right and left anterior (limbic) and posterior (motor) globus pallidus internus (GPI). RESULTS: Regardless of the anesthetic agent used (propofol or sevoflurane), both patients showed similar neurons firing rates in the four regions studied, namely the limbic and motor portions of the globus pallidus externus (GPE) or GPI. In both patients, firing rates were similar in the GPE (12.2+/-1.8 Hz, N=38) and GPI (13.2+/-1.0 Hz, N=83) portions of the limbic track, while the motor GPE fired at a higher frequency (23.8+/-2.7 Hz, N=18) than the motor GPI (12.5+/-1.4 Hz, N=23). CONCLUSIONS: These results demonstrate that light propofol or sevoflurane anesthesia influences pallidal activity in a similar way. Electrophysiological recordings suggest that Lesch-Nyhan syndrome might be characterized by analogous firing frequencies in the limbic GPE and GPI while motor GPE would tend to fire at higher rate than the motor GPI. It is therefore tempting to suggest that the symptoms that are observed in Lesch-Nyhan syndrome might result from motor GPI inhibition. SIGNIFICANCE: This observation may confirm the Albin and Delong's model of the basal nuclei in hypokinetic and hyperkinetic disorders.
Assuntos
Globo Pálido/fisiopatologia , Síndrome de Lesch-Nyhan/fisiopatologia , Sistema Límbico/fisiopatologia , Neurônios Motores/fisiologia , Criança , Terapia por Estimulação Elétrica , Eletrofisiologia/métodos , Humanos , Hipoxantina Fosforribosiltransferase/deficiência , Sono/fisiologiaRESUMO
BACKGROUND: Despite extensive discussion in recent years, brain biopsy in patients positive for human immunodeficiency virus who manifest cerebral mass lesions remains an ill-defined step in management. METHODS: Prebiopsy data of 26 human immunodeficiency virus-positive patients with cerebral mass lesions who underwent computed tomography-guided stereotactic brain biopsy (SBB) were reviewed by a specialist in infectious diseases and by a neuroradiologist to establish a clinical diagnosis and a treatment plan for each patient. The postbiopsy diagnosis was compared with the prebiopsy diagnosis. Long-term patient outcome after SBB was recorded by means of a clinical performance scale to estimate its impact on life expectancy and clinical performance. RESULTS: The SBB was diagnostic in 25 patients (96%). Potentially treatable disease was diagnosed in 21 patients (81%), and specific therapy was initiated in 17 patients (65%); 10 patients (39%) were able to complete therapy. The SBB corroborated the clinical diagnosis in 13 (52%) of 25 patients. The group with identical clinical and biopsy-proved diagnoses showed significantly better response to therapy (P = .02), clinical performance (P = .04), and survival after biopsy (P = .01), as compared with the group with different clinical and biopsy-proved diagnosis, although no significant difference was found for the degree of immunosuppression. Only completion of the treatment plan increased life expectancy significantly (P = .008). CONCLUSIONS: These data show that in human immunodeficiency virus-positive patients with brain mass lesions, SBB has a high diagnostic yield. A subgroup of patients will benefit from specific therapy guided by the SBB result. The procedure should, however, be strictly limited to patients able to tolerate specific therapy.
Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , Encefalopatias/virologia , Encéfalo/virologia , Síndrome da Imunodeficiência Adquirida/terapia , Adulto , Biópsia/métodos , Encéfalo/patologia , Encefalopatias/patologia , Encefalopatias/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas Estereotáxicas , Tomografia Computadorizada por Raios XRESUMO
Treating patients with Parkinson's disease is not an easy task for the physician who is facing a disease well responsive to symptomatic therapy, yet escaping any curative approaches. In spite of the large therapeutic armamentarium available, many issues remained unsolved, as indications of a particular therapeutic agent are only loosely defined and evolving according to various parameters such as disease progression and severity, the profile of potentially serious adverse effects, the physician's level of expertise and patient's expectations. The growing experience acquired with subthalamic nucleus deep brain stimulation has shown that indications for such a surgery have to be cautiously examined. After initial therapeutic enthusiasm, we are now at a time of problems and controversies.
Assuntos
Doença de Parkinson/terapia , Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/uso terapêutico , Antagonistas Muscarínicos/uso terapêuticoRESUMO
The prevalence of epilepsy is about 1%. Only two thirds of these patients respond satisfactorily to an antiepileptic drug (AED) treatment. New AED did not clearly improve this overall efficacy, but often show a better tolerability as compared to old AED. This may allow a more targeted choice, especially in some delicate clinical situations, such as for the treatment of women in childbearing age, or patients receiving other drugs with possible pharmacokinetic interactions. Invasive approaches should be considered early in the course of treatment-resistant epilepsy, and may offer a complete seizure remission in selected cases. On the background of recent acquisitions from the literature, the pros and cons of different treatment options are presented. This is followed by the discussion of some clinical relevant situations.
Assuntos
Epilepsia/terapia , Adulto , Anticonvulsivantes/uso terapêutico , Humanos , Procedimentos NeurocirúrgicosRESUMO
Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.
Assuntos
Astrócitos/citologia , Glioma/metabolismo , Substâncias de Crescimento/metabolismo , Líquidos Corporais/fisiologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Cistos/metabolismo , Glioma/patologia , Substâncias de Crescimento/farmacologia , Humanos , Interferon gama/análise , Interleucina-1/análise , Valores de Referência , SolubilidadeRESUMO
Physiologic and anatomic evidence suggest that 5-hydroxytryptamine (5-HT) neurons regulate local cerebral blood flow and blood-brain barrier permeability. To evaluate the possibility that some of these effects occur directly on the blood vessels, molecular and/or pharmacologic approaches were used to assess the presence of 5-HT receptors in human brain microvascular fractions, endothelial and smooth muscle cell cultures, as well as in astroglial cells which intimately associate with intraparenchymal blood vessels. Isolated microvessels and capillaries consistently expressed messages for the h5-HT1B, h5-HT1D, 5-HT1F, 5-HT2A but not 5-HT7 receptors. When their distribution within the vessel wall was studied in more detail, it was found that capillary endothelial cells exhibited mRNA for the h5-HT1D and for the 5-HT7 receptors whereas microvascular smooth muscle cells, in addition to h5-HT1D and 5-HT7, also showed polymerase chain reaction products for h5-HT1B receptors. Expression of 5-HT1F and 5-HT2A receptor mRNAs was never detected in any of the microvascular cell cultures. In contrast, messages for all 5-HT receptors tested were detected in human brain astrocytes with a predominance of the 5-HT2A and 5-HT7 subtypes. In all cultures, sumatriptan inhibited (35-58%, P < .05) the forskolin-stimulated production of cyclic AMP, an effect blocked by the 5-HT1B/1D receptor antagonists GR127935 and GR55562. In contrast, 5-carboxamidotryptamine induced strong increases (> or = 400%, P < .005) in basal cyclic AMP levels that were abolished by mesulergine, a nonselective 5-HT7 receptor antagonist. Only astroglial cells showed a ketanserin-sensitive increase (177%, P < .05) in IP3 formation when exposed to 5-HT. These results show that specific populations of functional 5-HT receptors are differentially distributed within the various cellular compartments of the human cortical microvascular bed, and that human brain astroglial cells are endowed with multiple 5-HT receptors. These findings emphasize the complex interactions between brain serotonergic pathways and non-neuronal cells within the CNS and, further, they raise the possibility that some of these receptors may be activated by antimigraine compounds such as brain penetrant triptan derivatives.
Assuntos
Astrócitos/metabolismo , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Endotélio Vascular/metabolismo , Microcirculação/metabolismo , Músculo Liso Vascular/metabolismo , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Colforsina/farmacologia , AMP Cíclico/metabolismo , Humanos , Neurônios/metabolismo , Isoformas de Proteínas/análise , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Serotonina/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sistemas do Segundo Mensageiro/efeitos dos fármacosRESUMO
A hallmark of invasive tumors is their ability to effect degradation of the surrounding extracellular matrix (ECM) by the local production of proteolytic enzymes, such as the matrix metalloproteases (MMPs). In this paper, we demonstrate that the invasion of human gliomas is mediated by a 72 kDa MMP, referred to as MMP-2, and provide further evidence that the activity of MMP-2 is regulated by protein kinase C (PKC). The invasiveness of five human glioma cell lines (A172, U87, U118, U251, U563) was assessed in an in vitro invasion assay and was found to correlate with the level of MMP-2 activity (r2 = 0.95); in contrast, the activity of this 72 kDa metalloprotease was barely detectable in non-invasive control glial cells (non-transformed human astrocytes and oligodendrocytes). Treatment with 1,10-phenanthroline, a metalloprotease inhibitor, or with a synthetic dipeptide, containing a blocking sequence (ala-phe) specific for MMPs, resulted in a > 90% reduction in glioma invasion. Furthermore, this MMP-2 activity could be inhibited by the treatment of tumor cells with calphostin C, a specific inhibitor of PKC. Glioma cell lines treated with calphostin C demonstrated a dose-dependent decrease (IC50 = 30 nM) in tumor invasiveness with a concomitant reduction in the activity of the MMP-2. Conversely, treatment of non-invasive control astrocytes with a PKC activator (phorbol ester) led to a corresponding increase in their invasiveness and metalloprotease activity. These findings support the postulate that MMP-2 activity constitutes an important effector of human glioma invasion and that the regulation of this proteolytic activity can be modulated by PKC.
Assuntos
Gelatinases/fisiologia , Glioma/patologia , Metaloendopeptidases/fisiologia , Invasividade Neoplásica , Proteína Quinase C/fisiologia , Divisão Celular , Colágeno/metabolismo , Colagenases/metabolismo , Combinação de Medicamentos , Inibidores Enzimáticos/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Gelatinases/antagonistas & inibidores , Glioma/enzimologia , Humanos , Laminina/metabolismo , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Metaloendopeptidases/antagonistas & inibidores , Naftalenos/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteoglicanas/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) of patients with PD allows reduction of antiparkinsonian medication but has only a mild direct effect on dyskinesia. Since antiparkinsonian medication has short- and long-term effects that may prevent an estimate of the maximal possible impact of STN DBS, such medication was used at the lowest possible dosage after DBS implantation. OBJECTIVE: To study the maximal and long-term effects of STN DBS using the lowest dose of medication. METHODS: Twenty consecutive patients with PD with motor fluctuations and dyskinesia underwent bilateral implantation under stereotactic guidance, microrecording, and clinical control. All medications were stopped before implantation and reintroduced, at the lowest dosage needed, only if the postoperative motor score did not reach the baseline level. Unified PD Rating Scale (UPDRS) motor (subscale III) scores were measured at baseline and after 3, 6, 12, and 24 months. RESULTS: After 21 plus minus 8 months, the UPDRS III "off-medication" score was decreased by 45% and was similar to the preoperative UPDRS III "on" score. Overall, medication was reduced by 79%, being completely withdrawn in 10 patients. Fluctuations and dyskinesia showed an overall reduction of >90%, disappearing completely in patients without medication. These improvements were maintained for 2 years. CONCLUSIONS: These results show that STN DBS could replace levodopa and allowed all antiparkinsonian medication to be discontinued in 50% of patients with PD. Fluctuations and dyskinesia disappeared completely in these patients but persisted in those still on medication. These improvements were maintained for 2 years.
Assuntos
Antiparkinsonianos/uso terapêutico , Terapia por Estimulação Elétrica , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Núcleo Subtalâmico/fisiologia , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
We studied 31 patients with histologically verified intracerebral cavernous angiomas. Twenty-two patients were symptomatic; nine were asymptomatic. All 22 symptomatic patients had seizures, three had intracranial hemorrhage, and one had signs of a space-occupying lesion. Twenty-seven lesions were located in the neocortex, three in the brainstem, and one in the cerebellum; all exhibited characteristic gross and microscopic features of cavernous angiomas. CT identified the location and extent of the lesion in 16 of 27 cases. Six of seven lesions demonstrated contrast enhancement, and ten of 27 scans harbored densities consistent with intracerebral calcium. Angiography was performed in 17 cases and was completely normal in eight. MRI revealed mixed signal intensity centrally with a ring of decreased signal intensity peripherally on T2-weighted images and was diagnostic in five cases. Surgical treatment offers an excellent prognosis for seizure control in patients with such lesions.
Assuntos
Hemangioma Cavernoso/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Hemangioma Cavernoso/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
We reviewed the prognostic significance of preoperative EEG findings in 25 patients who underwent functional hemispherectomy. Bilateral independent epileptogenic foci, found in five patients, generally indicate a less satisfactory outcome, with only three of the five patients becoming seizure free following hemispherectomy. In contrast, abnormalities of background activity over the "good" hemisphere, multifocal epileptic activity confined to the side of operation, or bilaterally synchronous discharges were associated with a good outcome and should not be considered as contraindications to operation. Postoperatively, discharges may occur in the functionally isolated frontal and occipital cortex, which are benign, with no other clinical significance than showing that the isolated cortex remains viable and continues to generate epileptogenic potentials.
Assuntos
Encéfalo/cirurgia , Epilepsia/cirurgia , Potenciais de Ação/fisiologia , Adolescente , Adulto , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Sincronização Cortical , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Lateralidade Funcional , Humanos , Lactente , Masculino , Período Pós-Operatório , PrognósticoRESUMO
A patient with severe postanoxic dystonia and bilateral necrosis of the basal ganglia, who was confined to a wheelchair, underwent bilateral ventralis oralis anterior deep brain stimulation (Voa-DBS) after 6 weeks of unsuccessful bilateral pallidal DBS (GPi-DBS). After 4 months of high intensity Voa-DBS, cognitively unimpaired, he showed major improvement in dystonia, became ambulant, but committed suicide. Brain examination confirmed the correct location of the electrodes in GPi and Voa on both sides.