Schwannomas vestibulares: experiencia en el tratamiento quirúrgico de 67 casos en 10 años / Vestibular schwannomas: surgical treatment of 67 cases in 10 years

Introducción: Los schwannomas vestibulares (SV) son tumores intracraneanos benignos, cuyo manejo actual es materia de debate, aunque el tratamiento microquirúrgico sigue siendo la modalidad de elección en la mayoría de los casos. Objetivo: Describir los resultados quirúrgicos de SV operados en un hospital público chileno. Material y método: Se presenta una serie de 67 pacientes tratados quirúrgicamente entre los años 2002 y 2012, en el Instituto de Neurocirugía Asenjo. Resultados: Sesenta y cinco casos (97%), correspondieron a tumores Koos III y IV, de los cuales el 52% fueron grandes (3-4 cm) o gigantes (> 4 cm). Se realizó acceso retrosigmoideo transmeatal en 41 casos (61%). Se logró exéresis total en el 97% y subtotal en el 3% de los casos. A los 6 meses de seguimiento promedio se obtuvo buena función facial (House-Brackmann I o II) en el 32,7% de los casos y función moderada (House-Brackmann III o IV) en el 42,3%. Las complicaciones cardiopulmonares fueron las más frecuentes (28%) y la mortalidad fue de 1,5%. Conclusiones: Los SV son tumores que pese a su naturaleza benigna pueden causar deterioro clínico significativo en estadios avanzados. Su tratamiento quirúrgico reviste gran complejidad, por lo que este debe ser realizado por equipos especializados para asegurar resultados funcionales óptimos

Introduction: Vestibular Schwannomas (VS) are benign intracranial tumors, for which their current management is a matter of debate, although microsurgical treatment remains the mode of choice in the majority of cases. Objective: To describe the surgical outcome of patients operated on for a VS in a Chilean Public Hospital. Material and method: A series of 67 patients treated surgically between 2002 and 2012, in the Institute of Neurosurgery Asenjo is presented. Results: Sixty-five cases (97%) corresponded to Koos III and IV tumors, of which 52% were large (3-4 cm) or Giant (> 4 cm). Forty-one cases were operated on using a retrosigmoid transmeatalapproach (61%). Total resection was achieved in 97% of the cases and subtotal in the remaining 3%. A mean six months follow-up showed that good facial function (House - Brackmann I or II) was obtained in 32.7% of the patients, and moderate function (House - Brackmann III or IV) in 42.3%. Cardiopulmonary complications were the most frequent (28%), and mortality was 1.5%. Conclusions: The VS are tumors that can cause significant neurological deficit in advanced stages, despite their benign nature. Surgical treatment is very complex, and must be performed by specialized teams to ensure optimal functional results

[Vestibular schwannomas: Surgical treatment of 67 cases in 10 years]. / Schwannomas vestibulares: experiencia en el tratamiento quirúrgico de 67 casos en 10 años.

INTRODUCTION: Vestibular Schwannomas (VS) are benign intracranial tumors, for which their current management is a matter of debate, although microsurgical treatment remains the mode of choice in the majority of cases. OBJECTIVE: To describe the surgical outcome of patients operated on for a VS in a Chilean Public Hospital. MATERIAL AND METHOD: A series of 67 patients treated surgically between 2002 and 2012, in the Institute of Neurosurgery Asenjo is presented. RESULTS: Sixty-five cases (97%) corresponded to Koos III and IV tumors, of which 52% were large (3-4 cm) or Giant (>4 cm). Forty-one cases were operated on using a retrosigmoid transmeatalapproach (61%). Total resection was achieved in 97% of the cases and subtotal in the remaining 3%. A mean six months follow-up showed that good facial function (House-Brackmann I or II) was obtained in 32.7% of the patients, and moderate function (House-Brackmann III or IV) in 42.3%. Cardiopulmonary complications were the most frequent (28%), and mortality was 1.5%. CONCLUSIONS: The VS are tumors that can cause significant neurological deficit in advanced stages, despite their benign nature. Surgical treatment is very complex, and must be performed by specialized teams to ensure optimal functional results.

Migración intracraneal de derivativa ventrículoperitoneal en paciente con hidranencefalia: reporte de un caso / Intracraneal migration of ventriculoperitoneal shunt in a patient with hydranecephaly: case report

La migración intracraneal de una derivativa ventrículo peritoneal (DVP) es una rara causa de disfunción valvular. Se presenta el caso de un paciente portador de hidranencefalia congénita con DVP desde el mes de vida, quien fue referido a neurocirugía a la edad de dos años y un mes por somnolencia, vómitos y bradicardia. El estudio con TC de encéfalo y radiografía de trayecto valvular revelaron migración intracraneal de su sistema derivativo, por lo que requirió cirugía de urgencia para retiro del sistema y reemplazo valvular. Inmediatamente posterior a la cirugía el paciente tuvo remisión completa de sus síntomas. A continuación se discuten los posibles mecanismos involucrados en su génesis y las medidas para evitar esta complicación

Intracranial migration of ventriculoperitoneal shunt is an extremely rare complication of hydrocephalus surgery. We present the case of a patient with congenital hydranencephaly treated with ventriculoperitoneal shunt installed elsewhere in the first month of life. He was referred to our center when he was 2 years old. The consulting symptoms were somnolency, vomiting and bradycardia. The image study consisted in a brain CT and chest x-ray that revealed the intracranial migration of his ventriculoperitoneal shunt. The patient was operated with the remotion of his shunting system and a complete new ventriculoperitoneal shunt was installed. Inmediately after surgery the patient had a complete remission of his symptoms. We reviewed the case due to the unusual of the complication and we discussed the possible mechanisms involved in its genesis and the measures to avoid it.

Antagonistic effects of TrkB and p75(NTR) on NMDA receptor currents in post-synaptic densities transplanted into Xenopus oocytes.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are essential regulators of synaptic function in the adult CNS. A TrkB-mediated effect at excitatory synapses is enhancement of NMDA receptor (NMDA-R)-mediated currents. Recently, opposing effects of TrkB and the pan-neurotrophin receptor p75(NTR) on long-term synaptic depression and long-term potentiation have been reported in the hippocampus. To further study the regulation of NMDA-Rs by neurotrophin receptors in their native protein environment, we micro-transplanted rat forebrain post-synaptic densities (PSDs) into Xenopus oocytes. One-minute incubations of oocytes with BDNF led to dual effects on NMDA-R currents: either TrkB-dependent potentiation or TrkB-independent inhibition were observed. Pro-nerve growth factor, a ligand for p75(NTR) but not for TrkB, produced a reversible, dose-dependent, TrkB-independent and p75(NTR)-dependent inhibition of NMDA-Rs. Fractionation experiments showed that p75(NTR) is highly enriched in the PSD protein fraction. Immunoprecipitation and pull-down experiments further revealed that p75(NTR) is a core component of the PSD, where it interacts with the PDZ3 domain of the scaffolding protein SAP90/PSD-95. Our data provide striking evidence for a rapid inhibitory effect of p75(NTR) on NMDA-R currents that antagonizes TrkB-mediated NMDA-R potentiation. These opposing mechanisms might be present in a large proportion of forebrain synapses and may contribute importantly to synaptic plasticity.

Electrophysiology and plasticity in isolated postsynaptic densities.

The organization and regulation of excitatory synapses in the mammalian CNS entails complex molecular and cellular processes. In the postsynaptic membrane, scaffolding proteins bring together glutamate receptors with multiple regulatory proteins involved in signal transduction. This gives rise to an elaborate postsynaptic structure known as the postsynaptic density (PSD). This protein network plays a critical role in the regulation of glutamate receptor function and thus in synaptic plasticity. To study this regulation, we have developed a system in which ionotropic glutamate receptors (iGluRs) can be recorded, in the steady state, by the patch clamp technique in isolated PSDs incorporated into giant liposomes. In this preparation, ionotropic glutamate receptors maintain their characteristic physiological and pharmacological properties. The recordings reflect the presence of channel clusters, as multiple conductance and subconductance states are observed. Each of the receptor subtypes is activated by a specific set of kinases that are activated differentially by Ca(2+): the "kainate receptor kinases" are active even in the presence of EGTA, i.e. they are not calcium-dependent; the "N-methyl-D-aspartate receptor (NMDAR) channel kinases" are active in the presence of submicromolar calcium concentrations, whereas the "alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor kinases" need microM calcium for activation. The NMDA receptor showed its characteristic voltage-dependent Mg(2+) blockade, and activation by phosphorylation was in part a consequence of a relief of Mg(2+) blockade. These results allow us to propose a model in which phosphorylation of NMDA receptors can contribute to a long-lasting and self-maintained change in synaptic function. The experimental approach we present will allow us to test the functional consequence of activation of the multiple signal transduction pathways thought to regulate excitatory neurotransmission in the adult CNS.

Protein kinase CK2 in postsynaptic densities: phosphorylation of PSD-95/SAP90 and NMDA receptor regulation.

Protein kinase CK2 (CK2) is highly expressed in rat forebrain where its function is not well understood. Subcellular distribution studies showed that the catalytic subunit of CK2 (CK2alpha) was enriched in postsynaptic densities (PSDs) by 68%. We studied the putative role of CK2 activity on N-methyl-D-aspartate receptor (NMDAR) function using isolated, patch-clamped PSDs in the presence of 2 mM extracellular Mg(2+). The usual activation by phosphorylation of the NMDARs in the presence of ATP was inhibited by the selective CK2 inhibitor 5,6-dichloro-1-beta-ribofuranosyl benzimidazole (DRB). This inhibition was voltage-dependent, i.e., 100% at positive membrane potentials, while at negative potentials, inhibition was incomplete. Endogenous CK2 substrates were characterized by their ability to use GTP as a phosphoryl donor and susceptibility to inhibition by DRB. Immunoprecipitation assays and 2D gels indicated that PSD-95/SAP90, the NMDAR scaffolding protein, was a CK2 substrate, while the NR2A/B and NR1 NMDAR subunits were not. These results suggest that postsynaptic NMDAR regulation by CK2 is mediated by indirect mechanisms possibly involving PSD-95/SAP90.

SH oxidation coordinates subunits of rat brain ryanodine receptor channels activated by calcium and ATP.

We have reported that ryanodine receptor (RyR) channels display three different responses to cytoplasmic free Ca2+ concentration ([Ca2+]) depending on their redox state (Marengo JJ, Hidalgo C, and Bull R. Biophys J 74: 1263-1277, 1998), with low, moderate, and high maximal fractional open times (Po). Activation by ATP of single RyR channels from rat brain cortex was tested in planar lipid bilayers with 10 or 0.1 microM cytoplasmic [Ca2+]. At 10 microM [Ca2+], low-Po channels presented lower apparent affinity to activation by ATP [[ATP] for half-maximal activation (KaATP) = 422 microM] than moderate-Po channels (KaATP = 82 microM). Oxidation of low-Po channels with thimerosal or 2,2'-dithiodipyridine (DTDP) gave rise to moderate-Po channels and decreased KaATP from 422 to 82 microM. At 0.1 microM cytoplasmic [Ca2+], ATP induced an almost negligible activation of low-Po channels. After oxidation to high-Po behavior, activation by ATP was markedly increased. Noise analysis of single-channel fluctuations of low-Po channels at 10 microM [Ca2+] plus ATP revealed the presence of subconductance states, suggesting a conduction mechanism that involves four independent subchannels. On oxidation the subchannels opened and closed in a concerted mode.

Epilepsy-induced changes in signaling systems of human and rat postsynaptic densities.

PURPOSE: To study seizure-induced changes in signaling proteins present in postsynaptic densities (PSDs) isolated from human epileptic neocortex and from rat cortex in which seizures were induced by injection of kainic acid. METHODS: We performed Western blot analysis of signaling proteins in PSDs isolated from cortical tissue. RESULTS: Seizures induce a strong upregulation of TrkB, the receptor for brain-derived neurotrophic factor (BDNF), whereas components of the N-methyl-d-aspartate (NMDA)-receptor complex are downregulated in both human and rat PSDs. CONCLUSIONS: These data show that long-term changes in PSD composition occur as a consequence of epileptic seizure activity.