Meningiomas and schwannomas: Molecular subgroup classification found by expression arrays

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

Reconstruction of bony facial contour deficiencies with polymethylmethacrylate implants: case report

Facial trauma can be considered one of the most serious aggressions found in the medical centers due to the emotional consequences and the possibility of deformity. In craniofacial surgery, the use of autologous bone is still the first choice for reconstructing bony defects or irregularities. When there is a shortage of donor bone or a patient refuses an intracranial operation, alloplastic materials such as polymethylmethacrylate (PMMA) can be used. The PMMA prosthesis can be pre-fabricated, bringing advantages such as reduction of surgical time, easy technical handling and good esthetic results. This paper describes the procedures for rehabilitating a patient with PMMA implants in the region of the face, recovering the facial contours and esthetics of the patient.

Ventilação oscilatória de alta freqüência em pediatria e neonatologia

Este trabalho teve por objetivo rever a literatura e descrever a utilização da ventilação oscilatória de alta freqüência em crianças e recém-nascidos. Revisão bibliográfica e seleção de publicações mais relevantes sobre ventilação de alta freqüência utilizando as bases de dados MedLine e SciElo publicadas nos últimos 15 anos. As seguintes palavras-chave foram utilizadas: ventilação oscilatória de alta freqüência, ventilação mecânica, síndrome do desconforto respiratório agudo, crianças e recém-nascidos. Descreveu-se o emprego da ventilação oscilatória de alta freqüência em crianças com síndrome do desconforto respiratório agudo, síndrome de escape de ar e doença pulmonar obstrutiva. Avaliou em recém-nascidos, síndrome do desconforto respiratório, displasia broncopulmonar, hemorragia peri-intraventricular, leucoencefalomalácia e extravasamento de ar. Também, abordou a transição da ventilação mecânica convencional para a ventilação de alta freqüência e o manuseio específico da ventilação de alta freqüência quanto à oxigenação, eliminação de gás carbônico, realização de exame radiológico, realização de sucção traqueal e utilização de sedação e bloqueio neuromuscular. Foram abordados o desmame deste modo ventilatório e as complicações. Em crianças maiores a ventilação oscilatória de alta freqüência é uma opção terapêutica, principalmente na síndrome do desconforto respiratório agudo, devendo ser empregada precocemente. Também pode ser útil em casos de síndrome de escape de ar e doença pulmonar obstrutiva. Em recém-nascidos, não há evidências que demonstram superioridade da ventilação oscilatória de alta freqüência em relação à ventilação convencional, sendo a síndrome de escape de ar a única situação clínica em que há evidência de melhores resultados com este modo ventilatório.

Morbidade hospitalar por causas externas no Município de São José dos Campos, Estado de São Paulo, Brasil

O objetivo dos estudo foi conhecer o perfil da morbidade das internações hospitalares por causas externas no Município de São José dos Campos, Estado de São Paulo, Brasil. Foram estudadas as internações pelo Sistema Único de Saúde (SUS) por lesões decorrentes de causas externas no primeiro semestre de 2003, no Hospital Municipal. Este hospital é a principal referência para o atendimento ao trama e foi responsável por 92,3% das internações pelo SUS por causas externas no período estudado. Entre os 873 pacientes internados, as lesões decorrentes de acidentes de transporte foram resposáveis por 31,8% dos casos, as quedas por 26,7% e as causas indeterminadas por 19,5%. A razão de masculinidade foi de 3,1:1 e a faixa etária predominante de 20-29 anos, com 23,3% das internações. As lesões mais freqüentes foram as fraturas (49,8%) e o traumatismo intracraniano (13,5%). Entre as fraturas, predominaram as do fêmur e as da perna, que representaram, respectivamente, 10,8% e 10,1%. A maior taxa de internação por local de residência ocorreu na região Norte do Município, com 470,0 internações por 100.000 habitantes. O perfil da morbidade hospitalar encontrado confirmou os acidentes de transporte como importante causa de internação hospitalar no Município e contrariou a tendência geral das quedas como principal causa externa de internação hospitalar. A distribuição por sexo, idade e natureza da lesão foi semelhante aos dados encontrados na literatura. A taxa de internação por causas externas por região de residência contribuiu para o mapeamento da violência em São José dos Campos-SP

Remote Cerebellar Hemorrhage (Zebra Sign) in Vascular Neurosurgery: Pathophysiological Insights

Hemorrhage in regions remote from the site of initial intracranial operations is rare, but may be fatal. Postoperative cerebellar hemorrhage as a complication of supratentorial surgery, with a radiological appearance known as zebra sign, is an increasingly recognized clinical entity and is associated mainly with vascular neurosurgery or temporal lobe resection. The pathophysiology remains unclear. Three cases of remote cerebellar hematoma occurred after neck clipping of anterior communicating artery aneurysms. All patients had similar clinical findings and underwent pterional craniotomy with the head in accentuated extension. One patient died and the two were discharged without symptoms. Cerebellar hemorrhage probably has a multifactorial origin involving positioning associated with abundant cerebrospinal fluid drainage causing cerebellar sag with resultant vein stretching and bleeding, and use of aspirin or other antiplatelet agents.

Polymorphisms and DNA methylation of gene TP53 associated with extra-axial brain tumors

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer; this gene is mutated in up to 50% of human tumors. It has a critical role in the cell cycle, apoptosis and cell senescence, and it participates in many crucial physiological and pathological processes. Polymorphisms of p53 have been suggested to be associated with genetically determined susceptibility in various types of cancer. Another process involved with the development and progression of tumors is DNA hypermethylation. Aberrant methylation of the promoter is an alternative epigenetic change in genetic mechanisms, leading to tumor suppressor gene inactivation. In the present study, we examined the TP53 Arg72Pro and Pro47Ser polymorphisms using PCR-RFLP and the pattern of methylation of the p53 gene by methylation-specific PCR in 90 extra-axial brain tumor samples. Patients who had the allele Pro of the TP53 Arg72Pro polymorphism had an increased risk of tumor development ( odds ratio, OR = 3.23; confidence interval at 95%, 95% CI = 1.71-6.08; P = 0.003), as did the allele Ser of TP53 Pro47Ser polymorphism (OR = 1.28; 95% CI = 0.03-2.10; P = 0.01). Comparison of overall survival of patients did not show significant differences. In the analysis of DNA methylation, we observed that 37.5% of meningiomas, 30% of schwannomas and 52.6% of metastases were hypermethylated, suggesting that methylation is important for tumor progression. We suggest that TP53 Pro47Ser and Arg72Pro polymorphisms and DNA hypermethylation are involved in susceptibility for developing extra-axial brain tumors.

Melatonin treatment decreases c-fos expression in a headache model induced by capsaicin

The aim of the present work was to analyze c-fos response within the trigeminal nucleus caudalis (TNC) of pinealectomized rats and animals that received intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to induce intracranial trigeminovascular stimulation. Experimental groups consisted of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1, diluted 1:50) only (VEI, n = 5); animals that received capsaicin solution (200 nM) only (CAP, n = 6); animals submitted to pinealectomy (PX, n = 5); sham-operated animals (SH, n = 5); animals submitted to pinealectomy followed by capsaicin stimulation (200 nM) after 15 days (PX + CAP, n = 7); and animals that received capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL, n = 5). Control rats, receiving vehicle in the cisterna magna, showed a small number of c-fos-positive cells in the TNC (layer I/II) as well as the sham-operated and pinealectomized rats, when compared to animals stimulated by capsaicin. On the other hand, pinealectomized rats, which received capsaicin, presented the highest number of c-fos-positive cells. Animals receiving capsaicin and melatonin treatment had similar expression of the vehicle group. Our data provide experimental evidence to support the role of melatonin and pineal gland in the pathophysiology of neurovascular headaches.

Charcot`s arthropathy secondary to herpetic encephalitis sequelae: an unusual presentation

Neuropathic arthropathy (Charcot`s arthropathy) is a progressive articular disease associated with a reduced sensorial and protector proprioceptive reflex. Its etiology includes many different conditions such as syringomyelia, traumatic lesion causing medullary deformity, spina bifida, diabetic neuropathy, leprosy neuropathy, neurofibromatosis, amyloid neuropathy, alcohol, and repetitive injection of hydrocortisone into joints, among others. However, the relationship between Charcot`s arthropathy and herpetic encephalitis has not yet been described. Herpes encephalitis causes acute and chronic diseases of the peripheral or central nervous system. It can manifest as subacute encephalitis, recurrent meningitis, or myelitis. It can also resemble psychiatric syndromes, diplopia, sensory changes in the face and limbs, personality changes, frontal dysexecutive syndrome, stiff neck, subclinical alterations of the vestibular function, intracranial hypertension, convulsion, hemiparesis, and generally includes motor components, among others. On the other hand, pure peripheral sensory disturbance has not been described. In this article, we report the clinical case of a patient with Charcot`s arthropathy secondary to pure peripheral sensory polyneuropathy as a consequence of progressive herpetic encephalitis sequelae. In this article, the authors report the first case of Charcot`s arthropathy secondary to herpetic encephalitis.

Microsurgical anatomy and approaches to the cavernous sinus

OBJECTIVE: The aim of this article is to describe the anatomy of the cavernous sinus and to provide a guide for use when performing surgery in this complex area. Clinical cases are used to illustrate routes to the cavernous sinus and its contents and to demonstrate how the cavernous sinus can be used as a pathway for exposure of deeper structures. METHODS: Thirty cadaveric cavernous sinuses were examined using X3 to X40 magnification after the arteries and veins were injected with colored silicone. Distances between the entrance of the oculomotor and trochlear nerves and the posterior clinoid process were recorded. Stepwise dissections (if the cavernous sinuses, performed to demonstrate the intradural and extradural routes, are accompanied by intraoperative photographs of those approaches. RESULTS: The anatomy of the cavernous sinus is complex because of the high density of critically important neural and vascular structures. Selective cases demonstrate how a detailed knowledge of cavernous sinus anatomy can provide for safer surgery with low morbidity. CONCLUSION: A precise understanding of the bony relationships and neurovascular contents of the cavernous sinus, together with the use of cranial base and microsurgical techniques, has allowed neurosurgeons to approach the cavernous sinus with reduced morbidity and mortality, changing the natural history of selected lesions in this region. Complete resection of cavernous sinus meningiomas has proven to be difficult and, in many cases, impossible without causing significant morbidity. However, surgical reduction of such lesions enhances the chances for success of subsequent therapy.

Follow-up of endovascular treatment of direct carotid-cavernous fistulas

Direct carotid-cavernous fistula (CCF) is a direct communication between the internal carotid artery (ICA) and the cavernous sinus. Some patients treated with detachable balloons develop pseudoaneurysms or present with a true aneurysm recanalization in the cavernous ICA with poorly known long-term radiological and clinical progression. The objective of the present study was to evaluate the long-term clinical and radiological progression of patients treated with detachable balloons. The present study evaluated 13 patients previously treated for direct CCF by an endovascular approach. The follow-up period ranged between 19 and 128 months. Ophthalmological evaluation demonstrated alterations in eight patients (61.5%). All of these alterations were already present from the moment of the treatment and displayed no signs of progression. Cranial magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) were performed in all patients, and 11 pseudoaneurysms were demonstrated in ten of the 11 patients in whom ICA patency had been preserved. Five patients were submitted for cerebral digital subtraction angiography (DSA) to characterize the pseudoaneurysms previously observed on MRA studies, with no significant differences in morphology, size, aneurismal neck, and number of lesions. Endovascular treatment of direct CCF with detachable balloons has been shown to be a long-term effective and stable therapeutic method. The authors found asymptomatic pseudoaneurysms in 91% of cases where the ICA patency was preserved. MRI and MRA demonstrated an accuracy similar to that of DSA in the diagnosis of pseudoaneurysms of cavernous ICA.

Fluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock

Background: Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Methods: Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer`s, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion (""clinical penumbra"") and from the corresponding contralateral side (""lesion`s mirror"") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Results: Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Conclusion: Both small volume hypertonic saline and large volume lactated Ringer`s blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Small volume resuscitation with 3% hypertonic saline solution decrease inflammatory response and attenuates end organ damage after controlled hemorrhagic shock

BACKGROUND: Recently, studies have been conducted examining the efficacy of 3% hypertonic saline solution (HS) for the treatment of traumatic brain injury; however, few studies have analyzed the effects of 3% hemorrhagic shock during hemorrhagic shock. The aim of this study was to test the potential immunomodulatory benefits of 3% hemorrhagic shock resuscitation over standard fluid resuscitation. METHODS: Wistar rats were bled to a mean arterial pressure of 35 mm Hg and then randomized into 3 groups: those treated with lactated Ringer`s solution (LR; 33 mL/kg, n = 7), 3% HS (10 mL/kg, n = 7), and 7.5% HS (4 mL/kg, n = 7). Half of the extracted blood was reinfused after fluid resuscitation. Animals that did not undergo shock served as controls (n = 5). Four hours after hemorrhagic shock, blood was collected for the evaluation of tumor necrosis factor-a and interleukin-6 by enzyme immunoassay. Lung and intestinal samples were obtained for histopathologic analysis. RESULTS: Animals in the HS groups had significantly higher mean arterial pressure than those in the LR group 1 hour after treatment. Osmolarity and sodium levels were markedly elevated in the HS groups. Tumor necrosis factor-alpha and interleukin-6 levels were similar between the control and HS groups but significantly higher in the LR group (P < .05). The lung injury score was significantly higher in the LR group compared with the 7.5% HS and 3% HS groups (5.7 +/- 0.7, 2.1 +/- 0.4, and 2.7 +/- 0.5, respectively). Intestinal injury was attenuated in the 7.5% HS and 3% HS groups compared with the LR group (2.0 +/- 0.6, 2.3 +/- 0.4, and 5.9 +/- 0.6, respectively). CONCLUSIONS: A small-volume resuscitation strategy modulates the inflammatory response and decreases end-organ damage after HS. Three percent HS provides immunomodulatory and metabolic effects similar to those observed with conventional concentrations of HS. (C) 2009 Elsevier Inc. All rights reserved.

Streptokinase and Enoxaparin as an Alternative to Fibrin-Specific Lytic-Based Regimens An ExTRACT-TIMI 25 Analysis

Background: Enoxaparin was superior to unfractionated heparin (UFH), regardless of fibrinolytic agent in ST-elevation myocardial infarction (STEMI) patients receiving fibrinolytic therapy in ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment Thrombolysis in Myocardial Infarction 25) trial. Objective: This post hoc analysis compared outcomes with streptokinase plus enoxaparin to the standard regimen of fibrin-specific lytic (FSL) plus UFH and to the newer combination of FSL plus enoxaparin. Methods: In ExTRACT-TIMI 25, STEMI patients received either streptokinase or a FSL (alteplase, reteplase or tenecteplase) at the physician`s discretion and were randomized to enoxaparin or UFH, stratified by fibrinolytic type. Thirty-day outcomes were adjusted for baseline characteristics, region, in-hospital percutaneous coronary intervention (PCI) and a propensity score for the choice of lytic. Results: The primary trial endpoint of 30-day death/myocardial infarction (MI) occurred in fewer patients in the streptokinase-enoxaparin cohort (n = 2083) compared with FSL-UFH (n = 8141) [10.2% vs 12.0%, adjusted odds ratio [OR(adj)] 0.76; 95% CI 0.62, 0.93; p = 0.008]. Major bleeding was significantly increased with streptokinase-enoxaparin compared with FSL-UFH (ORadj 2.74; 95% CI 1.81; 4.14; p < 0.001) but intracranial haemorrhage (ICH) was similar (OR(adj) 0.90; 95% CI 0.40, 2.01; p = 0.79). Net clinical outcomes, defined as either death/MI/major bleeding or as death/MI/ICH tended to favour streptokinase-enoxaparin compared with FSL-UFH (OR(adj) 0.88; 95% CI 0.73, 1.06; p = 0.17; and OR(adj) 0.77; 95% CI 0.63, 0.93; p = 0.008, respectively). Patients receiving FSL-enoxaparin (n = 8142) and streptokinase-enoxaparin therapies experienced similar adjusted rates of the primary endpoint (OR(adj) 1.08; 95% CI 0.87, 1.32; p = 0.49) and net clinical outcomes. Conclusions: Our results suggest that fibrinolytic therapy with the combination of streptokinase and the potent anticoagulant agent enoxaparin resulted in similar adjusted outcomes compared with more costly regimens utilizing a FSL.

INTENSITY-MODULATED AND 3D-CONFORMAL RADIOTHERAPY FOR WHOLE-VENTRICULAR IRRADIATION AS COMPARED WITH CONVENTIONAL WHOLE-BRAIN IRRADIATION IN THE MANAGEMENT OF LOCALIZED CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a ""boost"" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels., compared with 3D-CRT. Intensity-modulated radiotherapy provided of 20, 30, and 40 Gy, respectively statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment. (C) 2010 Elsevier Inc.

Ductus venosus Doppler and postnatal outcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries

Objective: To evaluate the relationship between ductus venosus Doppler findings on the day of delivery and postnatal outcomes in pregnancies with absent or reversed end-diastolic (ARED) flow in the umbilical arteries. Study design: Postnatal outcomes of 103 newborns of pregnancies with a diagnosis of ARED flow on Doppler velocimetry of the umbilical arteries were analyzed retrospectively between January 1997 and December 2004. Single pregnancies and fetuses without malformations were included. The cases were divided into two groups according to the flow during atrial contraction (a-wave) in the ductus venosus on the day of delivery: group A, 20 cases with absent or reversed flow in the ductus venosus and group B, 83 cases with positive flow. The results were analyzed statistically using the chi-square test, Fisher`s exact test and the Mann-Whitney U test with the level of significance set at 5%. Results: All newborns were delivered by cesarean section. Gestational age was similar in the two groups (group A: 30 weeks and group B: 30.9 weeks, P = 0.23). Absent or reversed ductus venosus flow was associated with the following adverse postnatal outcomes: lower birthweight (P < 0.001), lower Apgar scores in the first (P = 0.001) and fifth minute (P = 0.001), a higher frequency of orotracheal intubation (P = 0.001) and pH at birth less than 7.20 (P < 0.001), pulmonary hemorrhage (P = 0.03), thrombocytopenia (P = 0.02), hypoglycemia (P = 0.01), intracranial hemorrhage (P = 0.02), and postnatal death (P = 0.007). Conclusion: The study of ductus venosus flow may provide additional information regarding the best time for interruption of pregnancies with ARED flow in the umbilical arteries characterized by extreme prematurity. (C) 2008 Elsevier Ireland Ltd. All rights reserved.