Central nervous system stimulation therapies in phantom limb pain: a systematic review of clinical trials.

Phantom limb pain is a chronic pain syndrome that is difficult to cope with. Despite neurostimulation treatment is indicated for refractory neuropathic pain, there is scant evidence from randomized controlled trials to recommend it as the treatment choice. Thus, a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain. A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases. Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed. There were a total of 10 full-text articles retrieved and included in this review. Deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and motor cortex stimulation were the treatment strategies used in the selected clinical trials. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception, as well as to relieve anxiety and depression symptoms in phantom limb pain patients. Conversely, invasive approaches were considered the last treatment option as evidence in deep brain stimulation and motor cortex stimulation suggests that the value of phantom limb pain treatment remains controversial. However, the findings on use of these treatment strategies in other forms of neuropathic pain suggest that these invasive approaches could be a potential option for phantom limb pain patients.

Indicaciones y seguimiento domiciliario de la tos asistida mecánica en el paciente neuromuscular / Indications and domiciliary follow-up of mechanical insufflation-exsufflation in patients with neuromuscular disorders

Introducción: La insuflación-exuflación mecánica (MI-E) es una importante terapia respiratoria para el enfermo neuromuscular, pero existen pocos datos publicados en relación con su uso en el domicilio. Objetivo: Evaluar las características clínicas de los pacientes en los que se prescribe la MI-E y analizar su cumplimiento, seguridad y causas de retirada a largo plazo. Material y métodos: Estudio observacional retrospectivo de 78 adultos con enfermedad neuromuscular a los que se les prescribió MI-E a domicilio en un hospital de tercer nivel entre enero de 2009 y junio de 2015. Se describen las características clínicas y funcionales en el momento de la indicación de la terapia, la frecuencia y los parámetros de uso, los efectos secundarios, así como las causas de abandono de la terapia y la mortalidad. Resultados: La mayoría de los pacientes eran hombres (67%), con una mediana de edad de 58 años. El diagnóstico mayoritario fue la esclerosis lateral amiotrófica (45% de los casos). Tenían afectación bulbar moderada-grave el 36% y el 22% utilizaba el dispositivo solo en fase insuflatoria. El 14% de los pacientes eran portadores de traqueostomía y el 69% de los casos utilizaban también ventilación mecánica. El cuidador era mayoritariamente quien realizaba la técnica (86%), diariamente en el 73% de los casos. Desde la prescripción fallecieron el 38% de los pacientes, la mayoría afectados de esclerosis lateral amiotrófica (96%), con una mediana de supervivencia de 8 meses. En un 6% la MI-E se retiró por ineficacia. Se describió un solo caso de efecto secundario, que no contraindicó el uso de la terapia. Conclusiones: La MI-E prescrita a domicilio es una técnica segura, con cumplimiento adecuado, incluso en pacientes con afectación bulbar y asociada a ventilación mecánica. Se constata la dependencia del enfermo hacia su cuidador para su práctica

Introduction: Mechanical insufflation-exsufflation (MI-E) is an important respiratory therapy for neuromuscular disorders, but there are few published data on its use at home. Objective: To assess the clinical characteristics of patients prescribed MI-E, and to analyse compliance, safety, and causes for long-term withdrawal. Material and methods: Retrospective observational study of 78 adults with neuromuscular disorders who were prescribed MI-E at home in a third level hospital from January 2009 to June 2015. The clinical and functional characteristics when the therapy was indicated, the frequency and parameters of use, adverse effects and causes of withdrawal and mortality were evaluated. Results: Most patients were men (67%) with a median age of 58 years. The main diagnosis was amyotrophic lateral sclerosis (45% of cases). Moderate-severe bulbar involvement was present in 36%, and 22% used the device only in the insufflation phase. Fourteen percent of patients had a tracheostomy and 69% of the patients underwent mechanical ventilation. MI-E was mostly performed by the caregiver (86%), on a daily basis in 73% of the patients. After prescription, 38% patients died; most of these patients had amyotrophic lateral sclerosis (96%), with a median survival of 8 months. In 6%, MI-E was withdrawn due to ineffectiveness. An adverse effect was reported in only one patient and did not contraindicate the use of the therapy. Conclusions: In our experience, MI-E prescribed at home was well tolerated and safe, even in patients with bulbar involvement. Patients showed good compliance with MI-E alone or associated with mechanical ventilation, but required help from caregivers for its performance

Implantación bilateral en dos tiempos para estimulación cerebral profunda en el tratamiento de la enfermedad de Parkinson idiopática bilateral: resultados clínicos / Bilateral two-stage implantation for deep brain stimulation in the treatment of bilateral idiopathic Parkinson's disease: clinical outcomes

Objetivo. La implantación bilateral simultánea de electrodos en el núcleo subtalámico para la enfermedad de Parkinson idiopática (EPI) se asocia a una duración elevada de la intervención, alteraciones del lenguaje y confusión posquirúrgica; además, existe evidencia de mejoría ipsilateral tras la estimulación del núcleo subtalámico. Para optimizar el manejo perioperatorio se realiza un estudio prospectivo con estimulación cerebral profunda (ECP) en el núcleo subtalámico en dos procedimientos unilaterales consecutivos. Pacientes y métodos. Estudio prospectivo de 41 pacientes con EPI bilateral, con implantación de ECP en dos fases quirúrgicas unilaterales. Se analizan sus resultados clínicos según las escalas Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn y Yahr, y Schwab y England, así como sus complicaciones. Resultados. La edad media fue de 61 ± 7 años, 23 hombres. Cinco pacientes (12%) no fueron intervenidos del núcleo subtalámico contralateral por buen control. La media en la UPDRS motora y la Hoehn y Yahr en off farmacológico preoperatorio fue de 44 ± 14 y 3, respectivamente, y de 19 ± 8 y 1,8 a los seis meses de seguimiento. La mejoría media en la escala de Schwab y England en el preoperatorio y a los seis meses fue del 39%. Dos pacientes tuvieron confusión postoperatoria, y uno, disartria transitoria. Conclusiones. La ECP bilateral en dos etapas unilaterales fue una opción eficaz y con escasas complicaciones en nuestra serie de pacientes con EPI. El 10% de los pacientes no precisó electrodos contralaterales. Sería necesario un estudio aleatorizado en pacientes sometidos a cirugía bilateral en uno y dos tiempos para confirmar estos resultados (AU)

Aims. Simultaneous bilateral implantation of electrodes in the subthalamic nucleus for idiopathic Parkinson’s disease (IPD) is associated with long surgery time, language disorders and post-operative confusion. Moreover, there is evidence of ipsilateral improvement after stimulation of the subthalamic nucleus. In order to optimise perioperative management a prospective study is conducted with deep brain stimulation (DBS) in the subthalamic nucleus in two consecutive unilateral procedures. Patients and methods. We conducted a prospective study of 41 patients with bilateral IPD, with DBS implantation in two unilateral surgical phases. Its clinical outcomes are analysed according to the Unified Parkinson’s Disease Rating Scale (UPDRS), the Hoehn & Yahr, and the Schwab & England scales, together with their complications. Results. The mean age was 61 ± 7 years old, 23 males. Five patients (12%) did not undergo surgery of the contralateral subthalamic nucleus due to good control. The mean on the motor UPDRS and the Hoehn & Yahr in preoperative pharmacological off was 44 ± 14 and 3, respectively, and 19 ± 8 and 1.8 at six months’ follow-up. The mean improvement on the Schwab & England scale in the pre-operative period and at six months was 39%. Two patients suffered postoperative confusion, and one of them had transient dysarthria. Conclusions. Bilateral DBS in two unilateral stages was an effective option with few complications in our series of patients with IPD. 10% of the patients did not require contralateral electrodes. It would be necessary to conduct a randomized study in patients who underwent bilateral surgery in one and two stages in order to confirm these results (AU)

Asbestos-related disease in upholsterers.

Before its use was banned in developed countries, asbestos was widely applied in upholstery. However, the risk of asbestos diseases among upholsterers has only rarely been reported. In this case series, we present a first series of 6 workers employed in small workshops who developed several asbestos-related diseases, including pleural plaques, pleural fibrosis, and asbestosis. Exposures were intermittent and difficult to quantify, but lung asbestos content assessed by bronchoalveolar lavage was high in the 3 patients evaluated. In conclusion, upholstery work should be considered an at-risk occupation for developing asbestos-related diseases during the 20th century.

[Bilateral two-stage implantation for deep brain stimulation in the treatment of bilateral idiopathic Parkinson's disease: clinical outcomes]. / Implantacion bilateral en dos tiempos para estimulacion cerebral profunda en el tratamiento de la enfermedad de Parkinson idiopatica bilateral: resultados clinicos.

AIMS: Simultaneous bilateral implantation of electrodes in the subthalamic nucleus for idiopathic Parkinson's disease (IPD) is associated with long surgery time, language disorders and post-operative confusion. Moreover, there is evidence of ipsilateral improvement after stimulation of the subthalamic nucleus. In order to optimise perioperative management a prospective study is conducted with deep brain stimulation (DBS) in the subthalamic nucleus in two consecutive unilateral procedures. PATIENTS AND METHODS: We conducted a prospective study of 41 patients with bilateral IPD, with DBS implantation in two unilateral surgical phases. Its clinical outcomes are analysed according to the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr, and the Schwab and England scales, together with their complications. RESULTS: The mean age was 61 ± 7 years old, 23 males. Five patients (12%) did not undergo surgery of the contralateral subthalamic nucleus due to good control. The mean on the motor UPDRS and the Hoehn and Yahr in preoperative pharmacological off was 44 ± 14 and 3, respectively, and 19 ± 8 and 1.8 at six months' follow-up. The mean improvement on the Schwab and England scale in the pre-operative period and at six months was 39%. Two patients suffered post-operative confusion, and one of them had transient dysarthria. CONCLUSIONS: Bilateral DBS in two unilateral stages was an effective option with few complications in our series of patients with IPD. 10% of the patients did not require contralateral electrodes. It would be necessary to conduct a randomised study in patients who underwent bilateral surgery in one and two stages in order to confirm these results.

TITLE: Implantacion bilateral en dos tiempos para estimulacion cerebral profunda en el tratamiento de la enfermedad de Parkinson idiopatica bilateral: resultados clinicos.Objetivo. La implantacion bilateral simultanea de electrodos en el nucleo subtalamico para la enfermedad de Parkinson idiopatica (EPI) se asocia a una duracion elevada de la intervencion, alteraciones del lenguaje y confusion posquirurgica; ademas, existe evidencia de mejoria ipsilateral tras la estimulacion del nucleo subtalamico. Para optimizar el manejo perioperatorio se realiza un estudio prospectivo con estimulacion cerebral profunda (ECP) en el nucleo subtalamico en dos procedimientos unilaterales consecutivos. Pacientes y metodos. Estudio prospectivo de 41 pacientes con EPI bilateral, con implantacion de ECP en dos fases quirurgicas unilaterales. Se analizan sus resultados clinicos segun las escalas Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn y Yahr, y Schwab y England, asi como sus complicaciones. Resultados. La edad media fue de 61 ± 7 años, 23 hombres. Cinco pacientes (12%) no fueron intervenidos del nucleo subtalamico contralateral por buen control. La media en la UPDRS motora y la Hoehn y Yahr en off farmacologico preoperatorio fue de 44 ± 14 y 3, respectivamente, y de 19 ± 8 y 1,8 a los seis meses de seguimiento. La mejoria media en la escala de Schwab y England en el preoperatorio y a los seis meses fue del 39%. Dos pacientes tuvieron confusion postoperatoria, y uno, disartria transitoria. Conclusiones. La ECP bilateral en dos etapas unilaterales fue una opcion eficaz y con escasas complicaciones en nuestra serie de pacientes con EPI. El 10% de los pacientes no preciso electrodos contralaterales. Seria necesario un estudio aleatorizado en pacientes sometidos a cirugia bilateral en uno y dos tiempos para confirmar estos resultados.

Papel de la imagen por tensor de difusión en el estudio prequirúrgico de la epilepsia del lóbulo temporal / The role of diffusion tensor imaging in the pre-surgical study of temporal lobe epilepsy

Introducción. La imagen por tensor de difusión (DTI) es una técnica no invasiva que puede ser utilizada para evaluar la integridad de la sustancia blanca cerebral. Objetivo. Investigar la utilidad de la DTI en pacientes con epilepsia del lóbulo temporal (ELT) y ver su relación con la lateralización del foco epileptógeno en estos pacientes. Pacientes y métodos. Se analizan 11 pacientes diagnosticados de ELT según el protocolo de evaluación prequirúrgica de nuestra unidad de epilepsia, y libres de crisis a los dos años de la realización de una lobectomía temporal más amigdalohipocampectomía (técnica de Spencer). Como parte de su estudio preoperatorio, se realiza una resonancia magnética cerebral de 1,5 T con secuencia de tensor de difusión y se estudian, mediante un análisis basado en vóxel, las diferencias en la conectividad entre el hemisferio intervenido y el contralateral. Resultados. Comparado con el hemisferio contralateral, se observó una reducción de la anisotropía fraccional estadísticamente significativa (p < 0,05) en el cuerpo calloso, el cíngulo, el fascículo longitudinal superior, las radiaciones talámicas anteriores, la cápsula interna, los núcleos ventral lateral y pulvinar del tálamo, el fascículo frontooccipital inferior, el fascículo uncinado, el fascículo longitudinal inferior y el giro parahipocampal ipsilaterales al foco epileptógeno. Conclusiones. La caracterización de las anormalidades en la conectividad de la sustancia blanca cerebral, a través de la DTI en pacientes con ELT, puede tener un valor importante para la lateralización del foco epileptógeno en la evaluación prequirúrgica. Serían necesarios estudios con un número más elevado de pacientes para confirmar estos resultados (AU)

Introduction. Diffusion tensor imaging (DTI) is a non-invasive technique that can be used to assess the integrity of the white matter in the brain. Aims. To investigate the usefulness of DTI in patients with temporal lobe epilepsy (TLE) and to observe its relationship with lateralisation of the epileptogenic focus in these patients. Patients and methods. We analysed 11 patients diagnosed with TLE in accordance with the pre-surgical protocol of our epilepsy unit, and who were seizure-free two years after performing a temporal lobectomy plus amygdalohippocampectomy (Spencer technique). As part of their pre-operative study, a 1.5 T magnetic resonance brain scan with diffusion tensor imaging was performed. A voxel-based analysis was then employed to study the differences in connectivity between the hemisphere that underwent surgery and the contralateral hemisphere. Results. Compared with the contralateral hemisphere, a statistically significant reduction in fractional anisotropy (p < 0.05) was observed in the corpus callosum, the cingulate, the superior longitudinal fasciculus, the anterior thalamic radiations, the internal capsule, the ventral lateral and pulvinar nuclei of the thalamus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the inferior longitudinal fasciculus and the parahippocampal gyrus, all ipsilateral to the epileptogenic focus. Conclusions. The characterisation of the abnormalities in the connectivity of the cerebral white matter, by means of DTI in patients with TLE, can be a valuable aid for the lateralisation of the epileptogenic focus in the pre-surgical evaluation of these patients. Further studies with a higher number of patients would be needed to confirm these results (AU)

[The role of diffusion tensor imaging in the pre-surgical study of temporal lobe epilepsy]. / Papel de la imagen por tensor de difusion en el estudio prequirurgico de la epilepsia del lobulo temporal.

INTRODUCTION: Diffusion tensor imaging (DTI) is a non-invasive technique that can be used to assess the integrity of the white matter in the brain. AIMS: To investigate the usefulness of DTI in patients with temporal lobe epilepsy (TLE) and to observe its relationship with lateralisation of the epileptogenic focus in these patients. PATIENTS AND METHODS: We analysed 11 patients diagnosed with TLE in accordance with the pre-surgical protocol of our epilepsy unit, and who were seizure-free two years after performing a temporal lobectomy plus amygdalohippocampectomy (Spencer technique). As part of their pre-operative study, a 1.5 T magnetic resonance brain scan with diffusion tensor imaging was performed. A voxel-based analysis was then employed to study the differences in connectivity between the hemisphere that underwent surgery and the contralateral hemisphere. RESULTS: Compared with the contralateral hemisphere, a statistically significant reduction in fractional anisotropy (p < 0.05) was observed in the corpus callosum, the cingulate, the superior longitudinal fasciculus, the anterior thalamic radiations, the internal capsule, the ventral lateral and pulvinar nuclei of the thalamus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the inferior longitudinal fasciculus and the parahippocampal gyrus, all ipsilateral to the epileptogenic focus. CONCLUSIONS: The characterisation of the abnormalities in the connectivity of the cerebral white matter, by means of DTI in patients with TLE, can be a valuable aid for the lateralisation of the epileptogenic focus in the pre-surgical evaluation of these patients. Further studies with a higher number of patients would be needed to confirm these results.

TITLE: Papel de la imagen por tensor de difusion en el estudio prequirurgico de la epilepsia del lobulo temporal.Introduccion. La imagen por tensor de difusion (DTI) es una tecnica no invasiva que puede ser utilizada para evaluar la integridad de la sustancia blanca cerebral. Objetivo. Investigar la utilidad de la DTI en pacientes con epilepsia del lobulo temporal (ELT) y ver su relacion con la lateralizacion del foco epileptogeno en estos pacientes. Pacientes y metodos. Se analizan 11 pacientes diagnosticados de ELT segun el protocolo de evaluacion prequirurgica de nuestra unidad de epilepsia, y libres de crisis a los dos años de la realizacion de una lobectomia temporal mas amigdalohipocampectomia (tecnica de Spencer). Como parte de su estudio preoperatorio, se realiza una resonancia magnetica cerebral de 1,5 T con secuencia de tensor de difusion y se estudian, mediante un analisis basado en voxel, las diferencias en la conectividad entre el hemisferio intervenido y el contralateral. Resultados. Comparado con el hemisferio contralateral, se observo una reduccion de la anisotropia fraccional estadisticamente significativa (p < 0,05) en el cuerpo calloso, el cingulo, el fasciculo longitudinal superior, las radiaciones talamicas anteriores, la capsula interna, los nucleos ventral lateral y pulvinar del talamo, el fasciculo frontooccipital inferior, el fasciculo uncinado, el fasciculo longitudinal inferior y el giro parahipocampal ipsilaterales al foco epileptogeno. Conclusiones. La caracterizacion de las anormalidades en la conectividad de la sustancia blanca cerebral, a traves de la DTI en pacientes con ELT, puede tener un valor importante para la lateralizacion del foco epileptogeno en la evaluacion prequirurgica. Serian necesarios estudios con un numero mas elevado de pacientes para confirmar estos resultados.

Hematomas subdurales crónicos. Arquitectura interna del hematoma como predictor de recidiva / Chronic subdural haematomas. The internal architecture of the haematoma as a predictor of recurrence

Introducción. La arquitectura interna del hematoma subdural crónico (HSDC) es un factor muy importante que se debe tener en cuenta como predictor de recidiva. Objetivo. Analizar los factores posiblemente asociados a la recidiva de los HSDC, prestando especial atención a dicha arquitectura. Pacientes y métodos. Hemos revisado 147 pacientes tratados desde 2010 hasta 2013. Dividimos los HSDC en cuatro tipos de acuerdo con la clasificación de Nakaguchi de 2001. Además, hemos recogido diferentes características clínicas y las hemos sometido a análisis estadístico para evaluar su posible asociación con la tasa de recidiva de los HSDC. Resultados. La tasa de recidiva fue del 14,75% y la de mortalidad, del 4,76%. El tratamiento con anticoagulantes, el tipo de hematoma y el no usar drenaje subdural fueron factores de riesgo estadísticamente significativos para la recurrencia del HSDC. Según la arquitectura interna, la tasa de recidiva fue del 36,36% para el tipo separado, del 15,90% para el laminar, del 8,82% para el homogéneo y del 0% para el trabecular. Dicha tasa fue significativamente mayor en el tipo separado respecto al homogéneo y trabecular. Conclusiones. El tratamiento con anticoagulantes y el no usar drenaje subdural son factores de riesgo de recurrencia de HSDC. Además, la división de los HSDC de acuerdo con la clasificación de Nakaguchi puede ser útil para predecir el riesgo de recurrencia, ya que la tasa de recidiva del tipo separado fue significativamente mayor que la del resto de tipos (AU)

Introduction. The internal architecture of a chronic subdural haematoma (CSDH) is an important factor that must be taken into account as a predictor of recurrence. Aim. To analyse the factors that are possibly associated to the recurrence of CSDH, with special emphasis on the abovementioned architecture. Patients and methods. We reviewed 147 patients treated between 2010 and 2013. The CSDH were classified into four types, in accordance with Nakaguchi’s classification published in 2001. Moreover, we gathered different clinical characteristics and they were submitted to a statistical analysis in order to evaluate the possible association between them and the rate of recurrence of CSDH. Results. The rate of recurrence was 14.75% and the mortality rate was 4.76%. Treatment with anticoagulants, the type of haematoma and not using subdural drainage were statistically significant risk factors for the recurrence of CSDH. In terms of the internal architecture, the rate of recurrence was 36.36% for the separated type, 15.90% for the laminar type, 8.82% for the homogenous and 0% for the trabecular type. This rate was significantly higher in the separated type with respect to the homogenous and trabecular types. Conclusions. We have observed that treatment with anticoagulants and not using subdural drainage are risk factors for the recurrence of CSDH. Furthermore, dividing CSDH up in accordance with Nakaguchi’s classification can be useful for predicting the risk of relapse, since the rate of recurrence of the separated type was significantly greater than that of the other types (AU)

[Chronic subdural haematomas. The internal architecture of the haematoma as a predictor of recurrence]. / Hematomas subdurales cronicos. Arquitectura interna del hematoma como predictor de recidiva.

INTRODUCTION: The internal architecture of a chronic subdural haematoma (CSDH) is an important factor that must be taken into account as a predictor of recurrence. AIM: To analyse the factors that are possibly associated to the recurrence of CSDH, with special emphasis on the above-mentioned architecture. PATIENTS AND METHODS: We reviewed 147 patients treated between 2010 and 2013. The CSDH were classified into four types, in accordance with Nakaguchi's classification published in 2001. Moreover, we gathered different clinical characteristics and they were submitted to a statistical analysis in order to evaluate the possible association between them and the rate of recurrence of CSDH. RESULTS: The rate of recurrence was 14.75% and the mortality rate was 4.76%. Treatment with anticoagulants, the type of haematoma and not using subdural drainage were statistically significant risk factors for the recurrence of CSDH. In terms of the internal architecture, the rate of recurrence was 36.36% for the separated type, 15.90% for the laminar type, 8.82% for the homogenous and 0% for the trabecular type. This rate was significantly higher in the separated type with respect to the homogenous and trabecular types. CONCLUSIONS: We have observed that treatment with anticoagulants and not using subdural drainage are risk factors for the recurrence of CSDH. Furthermore, dividing CSDH up in accordance with Nakaguchi's classification can be useful for predicting the risk of relapse, since the rate of recurrence of the separated type was significantly greater than that of the other types.

TITLE: Hematomas subdurales cronicos. Arquitectura interna del hematoma como predictor de recidiva.Introduccion. La arquitectura interna del hematoma subdural cronico (HSDC) es un factor muy importante que se debe tener en cuenta como predictor de recidiva. Objetivo. Analizar los factores posiblemente asociados a la recidiva de los HSDC, prestando especial atencion a dicha arquitectura. Pacientes y metodos. Hemos revisado 147 pacientes tratados desde 2010 hasta 2013. Dividimos los HSDC en cuatro tipos de acuerdo con la clasificacion de Nakaguchi de 2001. Ademas, hemos recogido diferentes caracteristicas clinicas y las hemos sometido a analisis estadistico para evaluar su posible asociacion con la tasa de recidiva de los HSDC. Resultados. La tasa de recidiva fue del 14,75% y la de mortalidad, del 4,76%. El tratamiento con anticoagulantes, el tipo de hematoma y el no usar drenaje subdural fueron factores de riesgo estadisticamente significativos para la recurrencia del HSDC. Segun la arquitectura interna, la tasa de recidiva fue del 36,36% para el tipo separado, del 15,90% para el laminar, del 8,82% para el homogeneo y del 0% para el trabecular. Dicha tasa fue significativamente mayor en el tipo separado respecto al homogeneo y trabecular. Conclusiones. El tratamiento con anticoagulantes y el no usar drenaje subdural son factores de riesgo de recurrencia de HSDC. Ademas, la division de los HSDC de acuerdo con la clasificacion de Nakaguchi puede ser util para predecir el riesgo de recurrencia, ya que la tasa de recidiva del tipo separado fue significativamente mayor que la del resto de tipos.

[Massive hemorrhage due to nodular hyperplasia of Brunner's glands in antiphospholipid syndrome]. / Hemorragia masiva por hiperplasia nodular de glándulas de Brunner en el síndrome antifosfolipídico.

Gastrointestinal hemorrhage is an exceptional complication of antiphospholipid syndrome and most reported cases are secondary to ischemic lesions. Brunner's gland hyperplasia is an infrequent and usually asymptomatic condition that has been associated with chronic renal failure. We report a patient with primary antiphospholipid syndrome who, after mechanic heart valve replacement and while in a state of drug-induced anticoagulation, experienced a life-threatening upper gastrointestinal hemorrhage due to nodular hyperplasia of Brunner's glands. This entity may be considered in the differential diagnosis of upper gastrointestinal bleeding in patients with antiphospholipid syndrome, most of whom are treated with oral anticoagulatory drugs, and particularly in patients with chronic renal failure.

Thrombospondin mediates focal adhesion disassembly through interactions with cell surface calreticulin.

Thrombospondin induces reorganization of the actin cytoskeleton and restructuring of focal adhesions. This activity is localized to amino acids 17-35 in the N-terminal heparin-binding domain of thrombospondin and can be replicated by a peptide (hep I) with this sequence. Thrombospondin/hep I stimulate focal adhesion disassembly through a mechanism involving phosphoinositide 3-kinase activation. However, the receptor for this thrombospondin sequence is unknown. We now report that calreticulin on the cell surface mediates focal adhesion disassembly by thrombospondin/hep I. A 60-kDa protein from endothelial cell detergent extracts has homology and immunoreactivity to calreticulin, binds a hep I affinity column, and neutralizes thrombospondin/hep I-mediated focal adhesion disassembly. Calreticulin on the cell surface was confirmed by biotinylation, confocal microscopy, and by fluorescence-activated cell sorting analyses. Thrombospondin and calreticulin potentially bind through the hep I sequence, since thrombospondin-calreticulin complex formation can be blocked specifically by hep I peptide. Antibodies to calreticulin and preincubation of thrombospondin/hep I with glutathione S-transferase-calreticulin block thrombospondin/hep I-mediated focal adhesion disassembly and phosphoinositide 3-kinase activation, suggesting that calreticulin is a component of the thrombospondin-induced signaling cascade that regulates cytoskeletal organization. These data identify both a novel receptor for the N terminus of thrombospondin and a distinct role for cell surface calreticulin in cell adhesion.

EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway.

A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachments along with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruption of focal adhesions in fibroblasts. We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces the fraction of cells presenting focal adhesions from approximately 60% to approximately 30% within 10 minutes. The dose dependency of focal adhesion disassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in the presence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathways to determine whether these contribute to EGF-induced effects. We have previously demonstrated that phospholipase C(gamma) (PLCgamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find here that short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLCgamma or mobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLCgamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059 that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLCgamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.

Thrombospondin signaling of focal adhesion disassembly requires activation of phosphoinositide 3-kinase.

Thrombospondin is an extracellular matrix protein involved in modulating cell adhesion. Thrombospondin stimulates a rapid loss of focal adhesion plaques and reorganization of the actin cytoskeleton in cultured bovine aortic endothelial cells. The focal adhesion labilizing activity of thrombospondin is localized to the amino-terminal domain, specifically amino acids 17-35. Use of a synthetic peptide (hep I), containing amino acids 17-35 of thrombospondin, enables us to examine the signaling mechanisms specifically involved in thrombospondin-induced disassembly of focal adhesions. We tested the hypothesis that activation of phosphoinositide 3-kinase is a necessary step in the thrombospondin-induced signaling pathway regulating focal adhesion disassembly. Both wortmannin and LY294002, membrane permeable inhibitors of phosphoinositide 3-kinase activity, blocked hep I-induced disassembly of focal adhesions. Similarly, wortmannin inhibited hep I-mediated actin microfilament reorganization and the hep I-induced translocation of alpha-actinin from focal adhesion plaques. Hep I also stimulated phosphoinositide 3-kinase activity approximately 2-3-fold as measured in anti-phosphoinositide 3-kinase and anti-phosphotyrosine immunoprecipitates. Increased immunoreactivity for the 85-kDa regulatory subunit in anti-phosphotyrosine immunoprecipitates suggests that the p85/p110 form of phosphoinositide 3-kinase is involved in this pathway. In 32Pi-labeled cells, hep I increased levels of phosphatidylinositol (3,4,5)-trisphosphate, the major product of phosphoinositide 3-kinase phosphorylation. These results suggest that thrombospondin signals the disassembly of focal adhesions and reorganization of the actin cytoskeleton by a pathway involving stimulation of phosphoinositide 3-kinase activity.

Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly.

Focal adhesions are specialized regions of cell membranes that are foci for the transmission of signals between the outside and the inside of the cell. Intracellular signaling events are important in the organization and stability of these structures. In previous work, we showed that the counter-adhesive extracellular matrix proteins, thrombospondin, tenascin, and SPARC, induce the disassembly of focal adhesion plaques and we identified the active regions of these proteins. In order to determine the mechanisms whereby the anti-adhesive matrix proteins modulate cytoskeletal organization and focal adhesion integrity, we examined the role of protein kinases in mediating the loss of focal adhesions by these proteins. Data from these studies show that cGMP-dependent protein kinase is necessary to mediate focal adhesion disassembly triggered by either thrombospondin or tenascin, but not by SPARC. In experiments using various protein kinase inhibitors, we observed that selective inhibitors of cyclic GMP-dependent protein kinase, KT5823 and Rp-8-Br-cGMPS, blocked the effects of both the active sequence of thrombospondin 1 (hep I) and the alternatively-spliced segment (TNfnA-D) of tenascin-C on focal adhesion disassembly. Moreover, early passage rat aortic smooth muscle cells which have high levels of cGMP-dependent protein kinase were sensitive to hep I treatment, in contrast to passaged cGMP-dependent protein kinase deficient cells which were refractory to hep I or TNfnA-D treatment, but were sensitive to SPARC. Transfection of passaged smooth muscle cells with the catalytic domain of PKG I alpha restored responsiveness to hep I and TNfnA-D. While these studies show that cGMP-dependent protein kinase activity is necessary for thrombospondin and tenascin-mediated focal adhesion disassembly, kinase activity alone is not sufficient to induce disassembly as transfection of the catalytic domain of the kinase in the absence of additional stimuli does not result in loss of focal adhesions.

SPARC mediates focal adhesion disassembly in endothelial cells through a follistatin-like region and the Ca(2+)-binding EF-hand.

SPARC is a one of a group of extracellular matrix proteins that regulate cell adhesion through a loss of focal adhesion plaques from spread cells. We previously reported that SPARC reduced the number of bovine aortic endothelial (BAE) cells positive for focal adhesions [Murphy-Ullrich et al. (1991): J Cell Biol 115:1127-1136]. We have now characterized the effect of SPARC on the cytoskeleton of BAE cells. Addition of SPARC to spread BAE cells caused a dose-dependent loss of focal adhesion-positive cells, that was maximal at approximately 1 microgram/ml (0.03 microM). Consistent with the loss of adhesion plaques as detected by interference reflection microscopy, vinculin appeared diffuse and F-actin was redistributed to the periphery of cells incubated with SPARC. However, the distribution of the integrin alpha v beta 3 remained clustered in a plaque-like distribution. These data, and the observation that SPARC binds to BAE cells but not to the extracellular matrix, indicate that SPARC acts via interactions with cell surface molecules and not by steric/physical disruption of integrin-extracellular matrix ligands. To determine the region(s) of SPARC that mediate a loss of focal adhesions, we tested peptides from the four distinct regions of SPARC. The cationic, cysteine-rich peptide 2.1 (amino acids 54-73) and the Ca(2+)-binding EF-hand-containing peptide 4.2 (amino acids 254-273) were active in focal adhesion disassembly. Furthermore, antibodies specific for these regions neutralized the focal adhesion-labilizing activity of SPARC. These results are consistent with previous data showing that peptide 2.1 and 4.2 interact with BAE cell surface proteins and indicate that the loss of focal adhesions from endothelial cells exposed to SPARC is a receptor-mediated event.