Caio M. Matias

Fas, FasL, and cleaved caspases 8 and 3 in glioblastomas: a tissue microarray-based study.

This investigation analyzed the immunoexpression of FasL, Fas, cleaved caspase-8, and cleaved caspase-3 in glioblastomas. Formalin-fixed and paraffin-embedded glioblastoma tissues and control brain tissues from 97 patients were analyzed by tissue microarrays and immunohistochemistry. Patients with glioblastomas that were negative or weakly stained (<50% of cells positive) for cleaved caspase-8 had worse cancer-specific overall survival (median=8.5 months) than did patients with tumors that highly expressed cleaved caspase-8 (median=11.7 months; P=0.0325), independent of clinical variables. There was no association of other markers with survival, treatment, sex, age, tumor size, and primary site. Among the tumors, there were reasonable to good positive correlations between the expression of FasL and Fas (r=0.47) and between Fas and cleaved caspase-8 (r=0.41), and there were poor positive correlations between Fas and cleaved caspase-3 (r=0.26), FasL and cleaved caspase-8 (r=0.22), and cleaved caspase-8 and -3 (r=0.31). Our results suggest that Fas-Fas-ligand signal transduction could be inhibited, especially at the stage of caspase-8 activation, thereby establishing a major mechanism for evasion of apoptosis by these tumors. The absence or low expression of cleaved caspase-8 in the tumors was a negative prognostic indicator for patient survival.

“Rescue” of bilateral subthalamic stimulation by bilateral pallidal stimulation: case report

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) orglobus pallidus pars interna (GPi) is well established as a treatment for advanced Parkinsons disease. In general, one of the 2 targets is chosen based on the clinical features of each patient. Stimulation of both targets could be viewed as redundant, given that the 2 targets are directly connected. However, it is possible that each target has different mechanisms, with clinical effects mediated by orthodromic or antidromic stimulation. The authors report the case of a patient with severe Parkinsons disease who had previously undergone bilateral subthalamic stimulation with excellent benefits. However, he presented with significant worsening associated with disease progression and pharmacological treatment, and then underwent bilateral GPi DBS. Follow-up assessment was conducted clinically as well as through blinded ratings of video recordings. Pallidal DBS may be a safe and useful strategy to manage dystonic features and behavioral complications of subthalamic stimulation and pharmacological management. While combined stimulation was quite successful in the reported patient, further studies with larger samples and longer follow-up periods will be necessary before recommending the addition of pallidal DBS as a routine strategy for patients previously implanted with STN DBS.

Correlation among anatomic landmarks, location of subthalamic deep brain stimulation electrodes, stimulation parameters, and side effects during programming monopolar review

BACKGROUND: Clinical benefits of deep brain stimulation can be limited by the presence of side effects produced by current spread to adjacent structures. OBJECTIVE: To identify a correlation between coordinates for each individual contact, neighboring structures, and pattern of side effects. METHODS: Coordinates of the electrodes and anatomic landmarks were obtained with a stereotactic surgical planning software and were correlated with stimulation-related side effects by using univariate and multivariable analyses. RESULTS: Monopolar stimulation elicited capsular side effects (CSEs) in 208 of 316 contacts (65.8%) and noncapsular side effects (NCSEs) in 223 of 316 contacts (70.6%). The occurrence of CSEs was correlated with contact number (P = .009) and with the “Z” (P = .03), whereas voltage threshold to CSEs exhibited correlation with the internal capsule angle (P = .035). The occurrence of NCSEs was correlated with contact number (P = .005), “X” (P = .03), “Y” (P = .004), and the distance to the red nucleus (P = .001 and P = .003). There was correlation between voltage threshold to NCSEs and the internal capsule angle (P = .006), electrodes coronal angle (P = .02), “X” (P = .001), “Y” (P < .001), “Z” (P < .001), and the distances to the internal capsule (P = .02) and to the red nucleus (P = .004 and P < .001). CONCLUSION: A better understanding how patient anatomy, stimulation parameters, and lead location in relation to neighboring structures influence the occurrence of side effects can be useful to inform targeting strategies. ABBREVIATIONS: AC, anterior commissure CSE, capsular side effect DBS, deep brain stimulation IC, internal capsule MCP, midcommissural point NCSE, noncapsular side effect PC, posterior commissure PD, Parkinson disease PW, pulse width STN, subthalamic nucleus

Brain Shift and Pneumocephalus Assessment During Frame-Based Deep Brain Stimulation Implantation With Intraoperative Magnetic Resonance Imaging

BACKGROUND Brain shift and pneumocephalus are major concerns regarding deep brain stimulation (DBS). OBJECTIVE To report the extent of brain shift in deep structures and pneumocephalus in intraoperative magnetic resonance imaging (MRI). METHODS Twenty patients underwent bilateral DBS implantation in an MRI suite. Volume of pneumocephalus, duration of procedure, and 6 anatomic landmarks (anterior commissure, posterior commissure, right fornix [RF], left fornix [LF], right putaminal point, and left putaminal point) were measured. RESULTS Pneumocephalus varied from 0 to 32 mL (median = 0.6 mL). Duration of the procedure was on average 195.5 min (118-268 min) and was not correlated with the amount of pneumocephalus. There was a significant posterior displacement of the anterior commissure (mean = -1.1 mm, P < .001), RF (mean = -0.6 mm, P < .001), LF (mean = -0.7 mm, P < .001), right putaminal point (mean = -0.9 mm, P = .001), and left putaminal point (mean = -1.0 mm, P = .001), but not of the posterior commissure (mean = 0.0 mm, P = .85). Both RF (mean = -.7 mm, P < .001) and LF (mean = -0.5 mm, P < .001) were posteriorly displaced after a right-sided burr hole. There was a correlation between anatomic landmarks displacement and pneumocephalus after 2 burr holes (rho = 0.61, P = .007), but not after 1 burr hole (rho = 0.16, P = .60). CONCLUSION Better understanding of how pneumocephalus displaces subcortical structures can significantly enhance our intraoperative decision making and overall targeting strategy.

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer's disease-associated Aβ oligomers

BACKGROUND Slice cultures have been prepared from several organs. With respect to the brain, advantages of slice cultures over dissociated cell cultures include maintenance of the cytoarchitecture and neuronal connectivity. Slice cultures from adult human brain have been reported and constitute a promising method to study neurological diseases. Despite this potential, few studies have characterized in detail cell survival and function along time in short-term, free-floating cultures. NEW METHOD We used tissue from adult human brain cortex from patients undergoing temporal lobectomy to prepare 200 μm-thick slices. Along the period in culture, we evaluated neuronal survival, histological modifications, and neurotransmitter release. The toxicity of Alzheimers-associated Aβ oligomers (AβOs) to cultured slices was also analyzed. RESULTS Neurons in human brain slices remain viable and neurochemically active for at least four days in vitro, which allowed detection of binding of AβOs. We further found that slices exposed to AβOs presented elevated levels of hyperphosphorylated Tau, a hallmark of Alzheimers disease. COMPARISON WITH EXISTING METHOD(S) Although slice cultures from adult human brain have been previously prepared, this is the first report to analyze cell viability and neuronal activity in short-term free-floating cultures as a function of days in vitro. CONCLUSIONS Once surgical tissue is available, the current protocol is easy to perform and produces functional slices from adult human brain. These slice cultures may represent a preferred model for translational studies of neurodegenerative disorders when long term culturing in not required, as in investigations on AβO neurotoxicity.

Use of 3D Printing in Surgical Planning: Strategies for Risk Analysis and User Involvement

This report aimed at promoting communication among project participants (hospital personnel and medical residents), increasing autonomy in decision-making during surgical planning. The steps taken for neuro navigation on a head model produced by additive manufacturing were analyzed for quality and risk assessment. Danger related to each navigation step, expected event sequence, dangerous situation and damage were pinpointed. User involvement was required from each project participant. After technical description of model preparation (filling and target deployment), the following steps were described: 1. Biomodel fixation, 2. T1-weighted image acquisition, 3. Target planning, 4. Stereotactic procedure, 5. Tomography acquisition, 6. Accuracy verification, 7. Disassembly. Error sources were identified and standardized procedures were established. A series of proposals were listed to assure quality and reproducibility. We concluded that accuracy can be improved as materials and procedures used for stereotaxy are optimized.

Extra and intradural spinal Hemangioblastoma

Hemangioblastomas do sistema nervoso central sao lesoes de baixo grau de malignidade, altamente vascularizadas, que podem se apresentar esporadicamente ou associadas com a doenca de Von Hippel-Lindau. Hemangioblastomas extradurais sao incomuns e os extra e intradurais sao ainda mais raros. Este estudo usa um caso ilustrativo e revisao da literatura para discutir as dificuldades de considerar o diagnostico correto e selecionar a melhor abordagem cirurgica. Um paciente do sexo masculino, branco, com 57 anos de idade apresentou-se com mielopatia e radiculopatia de C5 a direita. As imagens mostraram lesao extra-intradural lobulada, em forma de ampulheta, com alta impregnacao apos contraste, que ocupava o canal vertebral e estreitava o forame intervertebral de C4-C5 a direita. A resseccao total da lesao intradural foi alcancada atraves de abordagem posterior, mas a porcao extradural so pode ser parcialmente removida. Melhora total dos sintomas foi observada apos quatro meses e o tumor residual tem sido seguido clinica e radiologicamente. Embora a impressao pre-operatoria tenha sido de um schwannoma espinal, o exame histopatologico revelou hemangioblastoma grau I, segundo a OMS. Apesar de sua raridade, exames complementares atuais permitem o correto diagnostico pre-operatorio. Isto e essencial para melhor programacao cirurgica, tendo em vista as caracteristicas particulares desta lesao.