La estimulación cerebral profunda en el trastorno obsesivo-compulsivo refractario al tratamiento: una revisión sistemática / Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: a systematic review

Introducción: Al menos el 10% de pacientes con trastorno obsesivo-compulsivo (TOC) son refractarios al tratamiento psicofarmacológico. La aparición de nuevas tecnologías neuroquirúrgicas (estimulación cerebral profunda[ECP]) de modulación de la actividad neuronal alterada está posibilitando su extensión a casos graves y refractarios de TOC en los que anteriormente se utilizaban técnicas quirúrgicas no reversibles. El objetivo de este artículo es revisar la evidencia científica existente sobre la eficacia y aplicabilidad de esta técnica en este grupo de pacientes. Método: Se ha realizado una revisión sistemática de la literatura en las bases de datos PubMed/Medline, Embase y PsycINFO usando las palabras clave relacionadas con «deep brain stimulation», «DBS» y «obsessive-compulsive disorder», «OCD». Dos de los autores seleccionaron los artículos, de manera independiente, a partir de sus abstracts y en función de si describían alguno de los aspectos principales de la técnica en el TOC: aplicabilidad; mecanismo de acción; dianas terapéuticas cerebrales; efectividad; efectos secundarios, y coterapias. Toda la información fue sistemáticamente extraída y evaluada. Resultados: El análisis crítico de la evidencia señala que la aplicación de la ECP en el tratamiento del TOC refractario está aportando resultados satisfactorios, con rangos asumibles de efectos secundarios. Sin embargo, todavía no hay evidencia suficiente que permita priorizar el uso de una determinada diana cerebral. La selección de pacientes ha de seguir un análisis de riesgo/beneficio, debiéndose individualizar la decisión de mantener un tratamiento concomitante farmacológico/psicoterapéutico. Conclusiones: La ECP se encuentra todavía en el ámbito de la investigación, pero su aplicación en el TOC-refractario es cada vez más frecuente, produciendo en la mayoría de los estudios una significativa mejoría de los síntomas, y también del funcionamiento y calidad de vida. Es preciso realizar más estudios controlados y aleatorizados sobre su efectividad a largo plazo, y sobre su relación riesgo/beneficio y costes

Introduction: At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. Method: We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. Results: The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. Conclusions: The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit

Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review. / La estimulación cerebral profunda en el trastorno obsesivo-compulsivo refractario al tratamiento: una revisión sistemática.

INTRODUCTION: At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. METHOD: We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. RESULTS: The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. CONCLUSIONS: The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit.

Pronóstico a largo plazo de la hidrocefalia crónica del adulto idiopática: I. Protocolo diagnóstico-terapéutico del Hospital Universitario Marqués de Valdecilla / Long-term prognosis of idiopathic chronic adult hydrocephalus: I. The University Hospital Marqués de Valdecilla diagnostic and therapeutic protocol

Introducción: A pesar de la existencia de guías clínicas desde hace más de una década, la complejidad diagnóstica y terapéutica de la hidrocefalia crónica del adulto idiopática hace que la variabilidad en su manejo sea elevada. Desarrollo: Se presenta el protocolo diagnóstico-terapéutico empleado en el Servicio de Neurocirugía del Hospital Universitario Marqués de Valdecilla para evaluar a los pacientes remitidos por sospecha diagnóstica de hidrocefalia crónica del adulto idiopática. El proceso diagnóstico incluye valoración neuropsicológica, RM craneal con secuencias de Cine-RM por contraste de fase, estudio urodinámico, registro continuo de presión intracraneal, hidrodinámica licuoral mediante test de infusión lumbar y medición de la presión intraabdominal. Se consideran candidatos quirúrgicos a los pacientes que cumplen cualquiera de los siguientes criterios: presión intracraneal media > 15 mmHg u ondas B en > 10% del registro nocturno; índice presión-volumen < 15 ml o resistencia al drenaje del líquido cefalorraquídeo (ROUT) > 4,5 mmHg/ml/min en el test de bolos; ROUT > 12 mmHg/ml/min, presión intracraneal > 22 mmHg o presencia de ondas B de alta amplitud en la meseta del test de Katzman; o respuesta a la evacuación licuoral de alto volumen. Conclusiones: La implementación de protocolos diagnóstico-terapéuticos podría mejorar varios aspectos del proceso asistencial de la hidrocefalia crónica del adulto idiopática, no solo al disminuir la variabilidad en la práctica clínica sino también al optimizar el uso de recursos sanitarios y ayudar a la identificación de áreas de incertidumbre científica, permitiendo dirigir los esfuerzos en investigación de una forma más adecuada

Introduction: Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. Development: The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marqués de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure > 15 mmHg, or B-waves present in >10% of overnight recording; pressure-volume index < 15 ml, or resistance to cerebrospinal fluid outflow (ROUT) > 4.5 mmHg/ml/min in bolus infusion test; ROUT >12 mmHg/ml/min, intracranial pressure > 22 mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high-volume cerebrospinal fluid withdrawal. Conclusions: The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way

[Long-term prognosis of idiopathic chronic adult hydrocephalus: I. The University Hospital Marqués de Valdecilla diagnostic and therapeutic protocol]. / Pronóstico a largo plazo de la hidrocefalia crónica del adulto idiopática: I. Protocolo diagnóstico-terapéutico del Hospital Universitario Marqués de Valdecilla.

INTRODUCTION: Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. DEVELOPMENT: The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marqués de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure >15mmHg, or B-waves present in >10% of overnight recording; pressure-volume index <15ml, or resistance to cerebrospinal fluid outflow (ROUT) >4.5mmHg/ml/min in bolus infusion test; ROUT >12mmHg/ml/min, intracranial pressure >22mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high-volume cerebrospinal fluid withdrawal. CONCLUSIONS: The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way.

Recovery of long-term paresis following resection of WHO grade II gliomas infiltrating the pyramidal pathway.

Recent publications had reported high rates of preoperative neurological impairments in WHO grade II gliomas (GIIG) that significantly affect the quality of life. Consequently, one step further in the analysis of surgical outcome in GIIG is to evaluate if surgery is capable to improve preoperative deficits. Here are reported two cases of GIIG infiltrating the primary motor cortex and pyramidal pathway that had a long-term paresis before surgery. Both patients were operated with intraoperative electrical stimulation mapping, with identification and preservation of the primary motor cortex and pyramidal tract. Despite the long-lasting paresis, both cases had a significant improvement of motor function after surgery. Knowledge of this potential recovery before surgery is of major significance for planning the surgical strategy in GIIG. Two possible predictors of motor recovery were analyzed: 1) reconstruction of the corticospinal tract with diffusion tensor imaging tractography is indicative of anatomo-functional integrity, despite tract deviation and infiltration; 2) intraoperative identification of motor response by electrostimulation confirms the presence of an intact peritumoral tract. Thus, resection should stop at this boundary even in cases of long lasting preoperative hemiplegia.

Stimulus-Evoked Electromyographic Monitoring During Minimally Invasive Transpedicular Implantation of Screws in Lumbosacral Spine: Threshold Value, Methodology and Clinical Effectiveness.

BACKGROUND: Stimulus-evoked electromyography (EMG) has been developed to increase the safety of transpedicular placement of screws. There is more consensus about this monitoring method in open surgery. Alarm thresholds for minimally invasive surgery are based on referential value for open surgery. Nevertheless, there are no uniform alarm criteria on this modality for minimally invasive surgery. Using an analysis of alarm threshold, methodology and clinical effectiveness on stimulus-evoked EMG monitoring for minimally invasive transpedicular implantation of screws in the lumbosacral spine, this study aims to reflect and recommend for optimizing accuracy. METHODS: Using a selection of studies, an analysis of the pedicle breach rates and breach-related clinical complication rates was made between studies on minimally invasive surgery by applying different thresholds. A second analysis of the pedicle breach rates and breach-related clinical complication rates was made between studies on open and minimally invasive surgery by applying the same threshold. RESULTS: In minimally invasive surgery, stimulus-evoked EMG has an acceptable accuracy in the detection of clinical relevant pedicle breaches. Suction limitation may alter the stimulation threshold. No significant differences in clinical effectiveness were observed between studies by applying thresholds of 5 mA, 7 mA, and 12 mA. However, a low threshold of 5 mA seems inappropriate for the tap stimulation. CONCLUSION: In minimally invasive surgery, continuous stimulation of instrumentation devices is recommended. A minimum 5-mA threshold should be used for stimulation of the pedicle access needle. Use of higher-stimulation thresholds during tapping and incorporation of an adapted continuous suction system may optimize the accuracy of stimulus-evoked EMG.

Insular Gliomas with Exophytic Extension to the Sylvian Cistern: A Glioma Growth Pattern That Has Gone Previously Unnoticed.

BACKGROUND: An exophytic tumor is defined as a tumor that has its epicenter in the nervous tissue but grows outside the anatomical superficial boundaries of the brain within an adjacent space. Exophytic extension of hemispheric gliomas is extremely rare. The object of this study is to describe the exophytic growth pattern of insular gliomas. METHODS: A series of 28 insular gliomas operated on consecutively were analyzed. The definition of exophytic glioma included these 2 criteria: 1) preoperative magnetic resonance imaging with evidence of exophytic local tumor extension outside the anatomical superficial boundaries of the brain; and 2) surgical identification of piamater and arachnoid invasion, with tumor growth to the adjacent cisterns. RESULTS: A series of 6 exophytic gliomas (21.4%) are reported, among a series of 28 consecutive insular gliomas operated. The exophytic component originated from the posterior portion of the basal frontal lobe, with extension to the sphenoidal compartment of the sylvian cistern, reaching the temporal pole. All exophytic tumors were type 5A in Yasargil classification. The histologic diagnosis was World Health Organization grade II glioma in 3 cases and anaplastic glioma in 3 cases. All patients underwent surgery, and the exophytic component was removed completely. CONCLUSIONS: Radiologic features that define the exophytic growth pattern in insular gliomas are the posterior displacement of the middle cerebral artery and a sharp subarachnoid margin that separates the exophytic tumor from the temporal pole. Contrary to the tumor that infiltrates the anterior perforating substance, the exophytic tumor is amenable for safe and complete resection.

Glioma exofítico hemisférico de muy lento crecimiento: a propósito de un caso / A very slow-growing exophytic hemisphere glioma: a case report

Introducción. Los gliomas de bajo grado presentan un patrón de crecimiento característico a través de las fibras de la sustancia blanca. El crecimiento exofítico en gliomas de bajo grado hemisféricos no se ha descrito previamente. Se presenta un caso de glioma hemisférico de lenta progresión y con crecimiento exofítico. Caso clínico. Varón de 55 años, con crisis parciales motoras secundarias a un oligodendroglioma de grado II de la Organización Mundial de la Salud. El tumor infiltraba la circunvolución frontal superior con extensión exofítica que se extendía por encima de la circunvolución precentral. Fue seguido con controles clinicorradiológicos durante 23 años. El análisis de la evolución radiológica del tumor demostraba un crecimiento tumoral lento, con una velocidad de crecimiento de 0,5 mm al año. Durante la exéresis quirúrgica se definió un plano subaracnoideo entre el componente exofítico y la circunvolución precentral, que se encontraba desplazada inferiormente sin infiltración tumoral. La estimulación eléctrica intraoperatoria no evidenció función en el componente exofítico, pero sí en la circunvolución precentral. No se observaron déficits neurológicos postoperatorios. Conclusiones. La velocidad de crecimiento en gliomas de bajo grado se ha estimado en 4-6 mm al año. El tumor que se describe aquí tiene una velocidad de crecimiento de 0,5 mm al año, muy por debajo de esta media. La identificación de la porción exofítica es un paso importante en la planificación preoperatoria. Este componente es más fácil de resecar debido al plano de clivaje subaracnoideo y a la ausencia de función (AU)

Introduction. Gliomas are characterized by a infiltrative pattern of growth, with cellular migration along the white matter fiber tracts, exophytic growth in low-grade gliomas has not been described yet. A case of hemispheric glioma with slow growing and an exophytic component is presented. Case report. 55 year-old male, with motor partial seizures. MRI shows a WHO grade II oligodendroglioma infiltrating the superior frontal gyrus with exophytic extension above the precentral gyrus. Clinical and radiological follow-up was performed for 23 years. Volumetric assessment of tumor progression revealed a growth rate of 0.5 mm per year. Surgical dissection revealed that the precentral gyrus was displaced inferiorly by the tumor, and a clear subarachnoid plane separated both structures. Functional areas were not identified within the exophytic component. Postoperative neurological deficits were not observed. Conclusions. The growth rate in low-grade gliomas has been estimated between 4 and 6 mm per year. The tumor described here had a growth rate of 0.5 mm per year, far below this average. Preoperative identification of this exophytic growth pattern is of major significance for surgical planning. The exophytic tumor is amenable for a safe and complete resection as it is covered by the arachnoid and pial membranes of the cistern and the surrounding brain (AU)

[A very slow-growing exophytic hemisphere glioma: a case report]. / Glioma exofítico hemisférico de muy lento crecimiento: a propósito de un caso.

INTRODUCTION: Gliomas are characterized by a infiltrative pattern of growth, with cellular migration along the white matter fiber tracts, exophytic growth in low-grade gliomas has not been described yet. A case of hemispheric glioma with slow growing and an exophytic component is presented. CASE REPORT: 55 year-old male, with motor partial seizures. MRI shows a WHO grade II oligodendroglioma infiltrating the superior frontal gyrus with exophytic extension above the precentral gyrus. Clinical and radiological follow-up was performed for 23 years. Volumetric assessment of tumor progression revealed a growth rate of 0.5 mm per year. Surgical dissection revealed that the precentral gyrus was displaced inferiorly by the tumor, and a clear subarachnoid plane separated both structures. Functional areas were not identified within the exophytic component. Postoperative neurological deficits were not observed. CONCLUSIONS: The growth rate in low-grade gliomas has been estimated between 4 and 6 mm per year. The tumor described here had a growth rate of 0.5 mm per year, far below this average. Preoperative identification of this exophytic growth pattern is of major significance for surgical planning. The exophytic tumor is amenable for a safe and complete resection as it is covered by the arachnoid and pial membranes of the cistern and the surrounding brain.

TITLE: Glioma exofitico hemisferico de muy lento crecimiento: a proposito de un caso.Introduccion. Los gliomas de bajo grado presentan un patron de crecimiento caracteristico a traves de las fibras de la sustancia blanca. El crecimiento exofitico en gliomas de bajo grado hemisfericos no se ha descrito previamente. Se presenta un caso de glioma hemisferico de lenta progresion y con crecimiento exofitico. Caso clinico. Varon de 55 años, con crisis parciales motoras secundarias a un oligodendroglioma de grado II de la Organizacion Mundial de la Salud. El tumor infiltraba la circunvolucion frontal superior con extension exofitica que se extendia por encima de la circunvolucion precentral. Fue seguido con controles clinicorradiologicos durante 23 años. El analisis de la evolucion radiologica del tumor demostraba un crecimiento tumoral lento, con una velocidad de crecimiento de 0,5 mm al año. Durante la exeresis quirurgica se definio un plano subaracnoideo entre el componente exofitico y la circunvolucion precentral, que se encontraba desplazada inferiormente sin infiltracion tumoral. La estimulacion electrica intraoperatoria no evidencio funcion en el componente exofitico, pero si en la circunvolucion precentral. No se observaron deficits neurologicos postoperatorios. Conclusiones. La velocidad de crecimiento en gliomas de bajo grado se ha estimado en 4-6 mm al año. El tumor que se describe aqui tiene una velocidad de crecimiento de 0,5 mm al año, muy por debajo de esta media. La identificacion de la porcion exofitica es un paso importante en la planificacion preoperatoria. Este componente es mas facil de resecar debido al plano de clivaje subaracnoideo y a la ausencia de funcion.

Incidence of Idiopathic Normal-Pressure Hydrocephalus in Northern Spain.

BACKGROUND: Although the incidence of idiopathic normal-pressure hydrocephalus (iNPH) can be 1.20 cases/1000 inhabitants/year in individuals ≥ 70 years old, in most series, the incidence of shunt-responsive iNPH appears to be <1/100,000 inhabitants/year. We report the results of a prospective 10-year longitudinal study of the incidence of iNPH in a northern Spanish population. METHODS: In a stable population of 590,000 inhabitants served by a single neurosurgical department, we periodically asked all primary care practitioners, neurologists, and geriatricians to refer for iNPH screening any patient with ventricular dilation who was complaining of motor disturbances, cognitive impairment, or sphincter dysfunction. RESULTS: From January 2003 to December 2012, 293 patients were referred with suspected normal-pressure hydrocephalus. In 187 patients, iNPH was diagnosed; 89 of these patients were classified as probable iNPH, and 98 were classified as possible iNPH. Cerebrospinal fluid diversion was performed in 152 patients, and 119 showed a good outcome. The incidence of iNPH was significantly greater in male patients and patients >60 years old and increased exponentially with age. After age 60, the standardized age- and sex-adjusted incidence rates for iNPH, shunt surgery for iNPH, and shunt-responsive iNPH were 13.36 cases/100,000 inhabitants/year, 10.85 cases/100,000 inhabitants/year, and 8.55 cases/100,000 inhabitants/year. No differences were detected in the response rate between probable and possible iNPH (80.52% vs. 76.00%; P = 0.497). CONCLUSIONS: Even with a protocol for patient referral in place, reported iNPH incidence was lower than predicted, reflecting a persistent problem of underdiagnosis in our population.

Epidemiology of Idiopathic Normal Pressure Hydrocephalus: A Systematic Review of the Literature.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is an important cause of gait disturbance and cognitive impairment in elderly adults. However, the epidemiology of iNPH is relatively unknown, largely as a result of the paucity of specifically designed population studies. This systematic review aims to assess the prevalence and incidence of iNPH. METHODS: A systematic literature review on the epidemiology of iNPH was conducted using MEDLINE/PubMed searching for articles published up to June 2014. RESULTS: The inclusion criteria were met by 21 studies. Of the studies, 12 were specifically designed for detecting cases of iNPH; however, only 4 were prospective. In people >65 years old, pooled prevalence obtained from specific population studies was 1.3%, which was almost 50-fold higher than that inferred from door-to-door surveys of dementia or parkinsonism. Prevalence may be higher in assisted-living and extended-care residents, with 11.6% of patients fulfilling the criteria for suspected iNPH and 2.0% of patients showing permanent improvement after cerebrospinal fluid diversion. The only prospective population-based survey that reported iNPH incidence estimated 1.20 cases/1000 inhabitants/year, 15-fold higher than estimates obtained from studies based on hospital catchment areas. The incidence of shunt surgery for iNPH and shunt-responsive iNPH obtained from incident cases of hospital catchment areas appears to be <2 cases/100,000 inhabitants/year and 1 case/100,000 inhabitants/year, respectively. No population-based study reporting the real values for these 2 parameters could be found. CONCLUSIONS: iNPH appears to be extremely underdiagnosed. Properly designed and adequately powered population-based studies are required to characterize the epidemiology of this disease accurately.

Subcortical anatomy as an anatomical and functional landmark in insulo-opercular gliomas: implications for surgical approach to the insular region.

OBJECT: Little attention has been given to the functional challenges of the insular approach to the resection of gliomas, despite the potential damage of essential neural networks that underlie the insula. The object of this study is to analyze the subcortical anatomy of the insular region when infiltrated by gliomas, and compare it with the normal anatomy in nontumoral hemispheres. METHODS: Ten postmortem human hemispheres were dissected, with isolation of the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus. Probabilistic diffusion tensor imaging (DTI) tractography was used to analyze the subcortical anatomy of the insular region in 10 healthy volunteers and in 22 patients with insular Grade II and Grade III gliomas. The subcortical anatomy of the insular region in these 22 insular gliomas was compared with the normal anatomy in 20 nontumoral hemispheres. RESULTS: In tumoral hemispheres, the distances between the peri-insular sulci and the lateral surface of the IFOF and uncinate fasciculus were enlarged (p < 0.05). Also in tumoral hemispheres, the IFOF was identified in 10 (90.9%) of 11 patients with an extent of resection less than 80%, and in 4 (36.4%) of 11 patients with an extent of resection equal to or greater than 80% (multivariate analysis: p = 0.03). CONCLUSIONS: Insular gliomas grow in the space between the lateral surface of the IFOF and uncinate fasciculus and the insular surface, displacing and compressing the tracts medially. Moreover, these tracts may be completely infiltrated by the tumor, with a total disruption of the bundles. In the current study, the identification of the IFOF with DTI tractography was significantly associated with the extent of tumor resection. If the IFOF is not identified preoperatively, there is a high probability of achieving a resection greater than 80%.

Fascículos asociativos ínsulo-operculares: revisión de su anatomía y de las implicaciones para el abordaje transopercular a la ínsula / Insular-opercular associative tracts: Review of their anatomy and relevance for the trans-opercular approach to the insula

INTRODUCCIÓN: No hay estudios que revisen en detalle y de forma sistemática la anatomía de los fascículos asociativos ínsulo-operculares. OBJETIVO: En el presente trabajo, se realizó una extensa revisión de la literatura reciente de las fibras de asociación relacionadas con el lóbulo de la ínsula y los opérculos. RESULTADOS: Los tractos conectados con los opérculos son el fascículo frontal oblicuo, el fascículo arcuato, la porción horizontal del fascículo longitudinal superior y el fascículo longitudinal medial. A nivel de la ínsula, el fascículo fronto-occipital inferior (FFOI) discurre paralelo al fascículo uncinado, atravesando la porción antero-inferior de la cápsula externa y el claustrum. CONCLUSIONES: La pars triangular y orbicular de la circunvolución frontal inferior y la parte media y anterior de la circunvolución temporal superior están menos conectadas con la red perisilviana asociativa. De esta forma, constituyen 2 corredores anatómicos para el abordaje transopercular a la ínsula

INTRODUCTION: The insula is a highly connected area, as an intricate network of afferent and efferent projections connect it with adjacent and distant cortical regions. Objective: To perform an extensive review of recent literature to analyse the anatomy of the associative tracts related to the insula. RESULTS: The frontal aslant tract, arcuate fasciculus, horizontal portion of the superior longitudinal fasciculus and the middle longitudinal fasciculus are associative tracts connected to the opercula. The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus run under the anterior and inferior portion of the insula. CONCLUSIONS: the pars triangularis and orbicularis of the inferior frontal gyrus, as well as the middle and anterior part of the superior temporal gyrus, have few connections with the perisylvian associative network. Consequently, in the trans-opercular approach to the insula, these 2 regions represent anatomical corridors that give access to the insula. The IFOF and the uncinate fasciculus represent the deep functional margin of resection

[Insular-opercular associative tracts: Review of their anatomy and relevance for the trans-opercular approach to the insula]. / Fascículos asociativos ínsulo-operculares: revisión de su anatomía y de las implicaciones para el abordaje transopercular a la ínsula.

INTRODUCTION: The insula is a highly connected area, as an intricate network of afferent and efferent projections connect it with adjacent and distant cortical regions. OBJECTIVE: To perform an extensive review of recent literature to analyse the anatomy of the associative tracts related to the insula. RESULTS: The frontal aslant tract, arcuate fasciculus, horizontal portion of the superior longitudinal fasciculus and the middle longitudinal fasciculus are associative tracts connected to the opercula. The inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus run under the anterior and inferior portion of the insula. CONCLUSIONS: the pars triangularis and orbicularis of the inferior frontal gyrus, as well as the middle and anterior part of the superior temporal gyrus, have few connections with the perisylvian associative network. Consequently, in the trans-opercular approach to the insula, these 2 regions represent anatomical corridors that give access to the insula. The IFOF and the uncinate fasciculus represent the deep functional margin of resection.

Culture dimensionality influences the resistance of glioblastoma stem-like cells to multikinase inhibitors.

Sunitinib, an inhibitor of kinases, including VEGFR and platelet-derived growth factor receptor (PDGFR), efficiently induces apoptosis in vitro in glioblastoma (GBM) cells, but does not show any survival benefit in vivo. One detrimental aspect of current in vitro models is that they do not take into account the contribution of extrinsic factors to the cellular response to drug treatment. Here, we studied the effects of substrate properties including elasticity, dimensionality, and matrix composition on the response of GBM stem-like cells (GSC) to chemotherapeutic agents. Thirty-seven cell cultures, including GSCs, parenchymal GBM cells, and GBM cell lines, were treated with nine antitumor compounds. Contrary to the expected chemoresistance of GSCs, these cells were more sensitive to most agents than GBM parenchymal cells or GBM cell lines cultured on flat (two-dimensional; 2D) plastic or collagen-coated surfaces. However, GSCs cultured in collagen-based three-dimensional (3D) environments increased their resistance, particularly to receptor tyrosine kinase inhibitors, such as sunitinib, BIBF1120, and imatinib. Differences in substrate rigidity or matrix components did not modify the response of GSCs to the inhibitors. Moreover, the MEK-ERK and PI3K-Akt pathways, but not PDGFR, mediate at least in part, this dimensionality-dependent chemoresistance. These findings suggest that survival of GSCs on 2D substrates, but not in a 3D environment, relies on kinases that can be efficiently targeted by sunitinib-like inhibitors. Overall, our data may help explain the lack of correlation between in vitro and in vivo models used to study the therapeutic potential of kinase inhibitors, and provide a rationale for developing more robust drug screening models.

Cellular plasticity confers migratory and invasive advantages to a population of glioblastoma-initiating cells that infiltrate peritumoral tissue.

Glioblastoma (GBM) is associated with infiltration of peritumoral (PT) parenchyma by isolated tumor cells that leads to tumor regrowth. Recently, GBM stem-like or initiating cells (GICs) have been identified in the PT area, but whether these GICs have enhanced migratory and invasive capabilities compared with GICs from the tumor mass (TM) is presently unknown. We isolated GICs from the infiltrated PT tissue and the TM of three patients and found that PT cells have an advantage over TM cells in two-dimensional and three-dimensional migration and invasion assays. Interestingly, PT cells display a high plasticity in protrusion formation and cell shape and their migration is insensitive to substrate stiffness, which represent advantages to infiltrate microenvironments of different rigidity. Furthermore, mouse and chicken embryo xenografts revealed that only PT cells showed a dispersed distribution pattern, closely associated to blood vessels. Consistent with cellular plasticity, simultaneous Rac and RhoA activation are required for the enhanced invasive capacity of PT cells. Moreover, Rho GTPase signaling modulators αVß3 and p27 play key roles in GIC invasiveness. Of note, p27 is upregulated in TM cells and inhibits RhoA activity. Gene silencing of p27 increased the invasive capacity of TM GICs. Additionally, ß3 integrin is upregulated in PT cells. Blockade of dimeric integrin αVß3, a Rac activator, reduced the invasive capacity of PT GICs in vitro and abrogated the spreading of PT cells into chicken embryos. Thus, our results describe the invasive features acquired by a unique subpopulation of GICs that infiltrate neighboring tissue.

Fiber dissection and diffusion tensor imaging tractography study of the temporoparietal fiber intersection area.

BACKGROUND: Lesion studies and recent surgical series report important sequelae when the inferior parietal lobe and posterior temporal lobe are damaged. Millions of axons cross through the white matter underlying these cortical areas; however, little is known about the complex organization of these connections. OBJECTIVE: To analyze the subcortical anatomy of a specific region within the parietal and temporal lobes where 7 long-distances tracts intersect, ie, the temporoparietal fiber intersection area (TPFIA). METHODS: Four postmortem human hemispheres were dissected, and 4 healthy hemispheres were analyzed through the use of diffusion tensor imaging--based tractography software. The different tracts that intersect at the posterior temporal and parietal lobes were isolated, and the relations with the surrounding structures were analyzed. RESULTS: Seven tracts pass through the TPFIA: horizontal portion of the superior longitudinal fasciculus, arcuate fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, optic radiations, and tapetum. The TPFIA was located deep to the angular gyrus, posterior portion of the supramarginal gyrus, and posterior portion of the superior, middle, and inferior temporal gyri. CONCLUSION: The TPFIA is a critical neural crossroad; it is traversed by 7 white matter tracts that connect multiple areas of the ipsilateral and contralateral hemisphere. It is also a vulnerable part of the network in that a lesion within this area will produce multiple disconnections. This is valuable information when a surgical approach through the parieto-temporo-occipital junction is planned. To decrease surgical risks, a detailed diffusion tensor imaging tractography reconstruction of the TPFIA should be performed, and intraoperative electric stimulation should be strongly considered.

Cost-utility of maximal safe resection of WHO grade II gliomas within eloquent areas.

BACKGROUND: Despite the growing use of intraoperative electrical stimulation (IES) mapping for resection of WHO grade II gliomas (GIIG) located within eloquent areas, some authors claim that this is a complex, time-consuming and expensive approach, and not well tolerated by patients, so they rely on other mapping techniques. Here we analyze the health related quality of life, direct and indirect costs of surgeries with and without intraoperative electrical stimulation (IES) mapping for resection of GIIG within eloquent areas. METHODS: A cohort of 11 subjects with GIIG within eloquent areas who had IES while awake (group A) was matched by tumor side and location to a cohort of 11 subjects who had general anesthesia without IES (group B). Direct and indirect costs (measured as loss of labor productivity) and utility (measured in quality adjusted life years, QALYs), were compared between groups. RESULTS: Total mean direct costs per patient were $38,662.70 (range $19,950.70 to $61,626.40) in group A, and $32,116.10 (range $22,764.50 to $46,222.50) in group B (p = 0.279). Total mean indirect costs per patient were $10,640.10 (range $3,010.10 to $86,940.70) in group A, and $48,804.70 (range $3,340.10 to $98,400.60) in group B (p = 0.035). Mean costs per QALY were $12,222.30 (range $3,801.10 to $47,422.90) in group A, and $31,927.10 (range $6,642.90 to $64,196.50) in group B (p = 0.023). CONCLUSIONS: Asleep-awake-asleep craniotomies with IES are associated with an increase in direct costs. However, these initial expenses are ultimately offset by medium and long-term costs averted from a decrease in morbidity and preservation of the patient's professional life. The present study emphasizes the importance to switch to an aggressive and safer surgical strategy in GIIG within eloquent areas.

Eficacia y seguridad del mapeo por estimulación eléctrica intraoperatoria para la extirpación de gliomas OMS grado ii y iii en áreas cerebrales elocuentes / Efficacy and safety of intraoperative electrical stimulation mapping for resection of WHO grade ii and iii gliomas within eloquent areas

Fundamento y objetivo: La técnica de mapeo por estimulación eléctrica intraoperatoria (EEI) es cada vez más utilizada para la extirpación de gliomas OMS grado ii (GGII) y iii (GGIII) en áreas elocuentes, pero son muy pocos los estudios que comparan esta técnica con la cirugía convencional (sin EEI). En este trabajo se compara el grado de resección tumoral, las secuelas, el control de la epilepsia y la calidad de vida en 2 series de pacientes operados con y sin mapeo por EEI.Pacientes y método: Se compararon los resultados en 2 series de pacientes operados de GGII y GGIII en áreas elocuentes en el mismo centro. Período A (2004-2009): 17 pacientes operados sin utilizar EEI. Período B (2009-2010): 19 pacientes operados utilizando EEI.Resultados: El porcentaje tumoral extirpado fue del 54,7% en el período A y del 79,9% en el período B (p=0,006). A los 6 meses de la cirugía, 8 pacientes del período A y uno del período B desarrollaron morbilidad neurológica (p=0,015; odds ratio [OR] 16, intervalo de confianza del 95% [IC 95%] 1,7-148,3). Dos pacientes del período A con epilepsia farmacorresistente y 8 del período B mejoraron el control de las crisis epilépticas (p=0,05; OR 42, IC 95% 2,1-825,7). Nueve pacientes del período A y 18 del período B volvieron a la misma situación laboral que antes de la cirugía (p=0,015; OR 16, IC 95% 1,7-148,4).Conclusiones: La comparación entre las cirugías convencional y con mapeo por EEI revela que esta última aumenta el grado de resección tumoral en un 25,2%, reduce el riesgo de secuelas permanentes en un 48,1%, mejora el control de la epilepsia en formas farmacorresistentes y preserva la calidad de vida (AU)

Background and objective: Despite the growing use of intraoperative electrical stimulation (IES) mapping for the resection of WHO grade ii and iii gliomas (GGII and GGIII) in eloquent areas, few studies have compared 2 series with and without IES. The present study compares 2 series of patients operated with and without IES at the same institution, analyzing the extent of resection, neurological morbidity, epilepsy prognosis and quality of life.Patients and methods: The surgical results in 2 series of patients with GGII and GGIII within eloquent were compared. Period A (2004-2009): 17 patients operated without IES. Period B (2009-2010): 19 patients operated with IES. Results: The extent of tumor resection was 54.7% in group A and 79.9% in group B (P=.006). Six months after surgery, neurological morbidity was present in 8 patients of group A and one patient of group B (P=.015; odds ratio [OR] 16, 95% confidence interval [95% CI] 1.7-148.3). Two patients of group A with refractory epilepsy, and 8 patients of group B improved epilepsy control (P=.05; OR 42, 95% CI 2.1-825.7). Nine patients of group A and 18 patients of group B returned to the same socio-professional situation as before surgery (P=.015; OR 16, 95% CI 1.7-148.4). Conclusions: The comparison of IES mapping surgery to conventional surgery revealed that the former enables to: increase in 25.2% the extent of tumor resection, decrease in 48.1% the risk of permanent sequelae, improve epilepsy control and preserve quality of life (AU)