Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Microsurgical treatment of trigeminal neuralgia in patients older than 70 years: An efficacy and safety study. / Tratamiento microquirúrgico de la neuralgia trigeminal en mayores de 70 años, estudio de eficacia y seguridad.

INTRODUCTION: The increasing incidence of trigeminal neuralgia (TN) with age together with population ageing call for reexamination of surgical treatment options for refractory TN in elderly patients. METHODS: Retrospective review of a consecutive series of patients older than 70 who underwent microvascular decompression (MVD) for refractory TN between 1997 and 2015. Outcomes based on the Barrow Neurological Institute pain intensity score (BNI score) and surgical complications were compared to those of patients younger than 70 undergoing MVD in the same period. RESULTS: Forty patients older than 70 (mean = 74.8 years) underwent interventions. At a mean follow-up time of 34 months, 73% of the patients presented complete absence of pain without medication (BNI I) and 85% had good pain control with or without medication (BNI I-III). A comparison of these patients with the 85 patients younger than 70 treated surgically during the same period did not find a significant association between age and achievement of pain control (BNI I-II). However, there was a significant association between age older than 70 and complete pain relief (BNI I; P=.03). The mean hospital stay in patients over 70 was also significantly longer (P=.04), although the postsurgical complication rate was similar to that in younger patients. CONCLUSIONS: Elderly patients with refractory TN may benefit from treatment with MVD and the probability of success and surgical risk are comparable to those in younger patients.

Survival analysis in high-grade glioma: The role of salvage surgery.

OBJECTIVES: This study addresses the survival of consecutive patients with high-grade gliomas (HGG) treated at the same institution over a period of 10 years. We analyse the importance of associated factors and the role of salvage surgery at the time of progression. METHODS: We retrospectively analysed a series of patients with World Health Organization (WHO) grade III/IV gliomas treated between 2008 and 2017 at Hospital Gregorio Marañón (Madrid, Spain). Clinical, radiological, and anatomical pathology data were obtained from patient clinical histories. RESULTS: Follow-up was completed in 233 patients with HGG. Mean age was 62.2 years. The median survival time was 15.4 months. Of 133 patients (59.6%) who had undergone surgery at the time of diagnosis, 43 (32.3%) underwent salvage surgery at the time of progression. This subgroup presented longer overall survival and survival after progression. Higher Karnofsky Performance Status score at diagnosis, a greater extent of surgical resection, and initial diagnosis of WHO grade III glioma were also associated with longer survival. CONCLUSIONS: About one-third of patients with HGG may be eligible for salvage surgery at the time of progression. Salvage surgery in this subgroup of patients was significantly associated with longer survival.

Treatment of neuropathic deafferentation pain using DREZ lesions; long-term results.

INTRODUCTION: Deafferentation pain secondary to spinal cord injury, brachial plexus avulsion and other peripheral nerve injuries is often refractory to conventional treatments. This study evaluates the long-term efficacy of spinal DREZ (Dorsal Root Entry Zone) lesions for the treatment of neuropathic pain syndromes caused by deafferentation. PATIENTS AND METHODS: A series of 18 patients with refractory deafferentation pain treated with radiofrequency DREZ lesions is presented. The immediate and long-term efficacy was measured with the Visual Analogue Scale (VAS) before and after treatment, the patient's subjective evaluation, the percentage of patients returning to work and the reduction in pain medication. RESULTS: Pain on the VAS significantly decreased from 8.6 preoperatively to 2.9 (p<.001) at discharge. Over the long-term, with a mean follow-up of 28 months (6-108) pain remained at 4.7 on the VAS (p<0.002). The percentage of patients with moderate to excellent pain relief was 77% at discharge and 68% at the last follow-up. Pain medication was reduced in 67% of the patients and 28% returned to work. The best results were obtained in patients with brachial plexus avulsion, with a significant long-term pain relief in all cases. CONCLUSIONS: Radiofrequency DREZ lesion is an effective and safe treatment for refractory neuropathic pain caused by deafferentation.

Dumbbell-shaped thoracic chondroid chordoma mimicking a neurinoma.

A 31-year-old woman was admitted to the hospital with paraparesis and pyramidal signs. Magnetic resonance imaging disclosed a homogeneously enhanced mass occupying the spinal canal at the T1-T2 level and extending to the apical pleural space through the right intervertebral foramen. Surgical resection was achieved using a laminectomy and complete facetectomy. Histological examination indicated chondroid chordoma. The patient received postoperative proton radio-therapy. Chondroid chordoma is a subtype of chordomas with better prognosis, and it may appear as a dumbbell-shaped tumor as previously described in classical chordomas.

Survival analysis in high-grade glioma: the role of salvage surgery. / Análisis de supervivencia en gliomas de alto grado: papel de la cirugía de rescate.

OBJECTIVES: This study addresses the survival of consecutive patients with high-grade gliomas treated at the same institution over a period of 10 years. We analyse the importance of associated factors and the role of salvage surgery at the time of progression. METHODS: We retrospectively analysed a series of patients with World Health Organization (WHO) grade III/IV gliomas treated between 2008 and 2017 at Hospital Gregorio Marañón (Madrid, Spain). Clinical, radiological, and anatomical pathology data were obtained from patient clinical histories. RESULTS: Follow-up was completed in 233 patients with HGG. Mean age was 62.2 years. The median survival time was 15.4 months. Of 133 patients (59.6%) who had undergone surgery at the time of diagnosis, 43 (32.3%) underwent salvage surgery at the time of progression. This subgroup presented longer overall survival and survival after progression. Higher Karnofsky Performance Status score at diagnosis, a greater extent of surgical resection, and initial diagnosis of WHO grade III glioma were also associated with longer survival. CONCLUSIONS: About one-third of patients with HGG may be eligible for salvage surgery at the time of progression. Salvage surgery in this subgroup of patients was significantly associated with longer survival.

Análisis de supervivencia en gliomas de alto grado: papel de la cirugía de rescate / Survival analysis in high-grade glioma: the role of salvage surgery

Objetivos: Analizar la supervivencia en el grupo de pacientes con gliomas de alto grado tratados de forma consecutiva en un mismo centro a lo largo de 10 años. Establecer la relevancia de los factores asociados y el papel de la cirugía de rescate en el momento de la progresión.MétodosFueron analizados de forma retrospectiva los pacientes con gliomas grado III y IV de la Organización Mundial de la Salud (OMS) diagnosticados en el Hospital Gregorio Marañón desde el 1 de enero de 2008 hasta el 31 de diciembre de 2017. Se obtuvieron de la historia clínica los datos clínicos, radiológicos y anatomopatológicos.ResultadosSe completó el seguimiento en 233 pacientes con diagnóstico de glioma de alto grado (III o IV de la OMS). La edad media fue de 62,2 años. La mediana de supervivencia se situó en 15,4 meses. De los 133 pacientes (59,6%) que habían sido intervenidos mediante cirugía resectiva en el momento del diagnóstico, en 43 (32,3%) se efectuó cirugía de rescate en el momento de la progresión. La supervivencia global, así como la supervivencia tras la progresión, resultó mayor en este subgrupo de pacientes. Otras variables relacionadas con una mayor supervivencia fueron la puntuación en la escala de Karnofsky, el grado de resección quirúrgica y el diagnóstico inicial de grado III de la OMS.ConclusionesAlrededor de una tercera parte de los pacientes con gliomas de alto grado pueden ser candidatos a una cirugía de rescate en el momento de la progresión. Ello está asociado a una mayor supervivencia. (AU)

Objectives: This study addresses the survival of consecutive patients with high-grade gliomas treated at the same institution over a period of 10 years. We analyse the importance of associated factors and the role of salvage surgery at the time of progression.MethodsWe retrospectively analysed a series of patients with World Health Organization (WHO) grade III/IV gliomas treated between 2008 and 2017 at Hospital Gregorio Marañón (Madrid, Spain). Clinical, radiological, and anatomical pathology data were obtained from patient clinical histories.ResultsFollow-up was completed in 233 patients with HGG. Mean age was 62.2 years. The median survival time was 15.4 months. Of 133 patients (59.6%) who had undergone surgery at the time of diagnosis, 43 (32.3%) underwent salvage surgery at the time of progression. This subgroup presented longer overall survival and survival after progression. Higher Karnofsky Performance Status score at diagnosis, a greater extent of surgical resection, and initial diagnosis of WHO grade III glioma were also associated with longer survival.ConclusionsAbout one-third of patients with HGG may be eligible for salvage surgery at the time of progression. Salvage surgery in this subgroup of patients was significantly associated with longer survival. (AU)

[Immunotherapy in high grade astrocytomas: principles and current state]. / Immunoterapia en astrocitomas de alto grado: principios y estado actual

It is generally accepted that tumour development promotes a systemic response leading to protect the host against cancer. However, tumours may as well elicit a partial immunodeficiency to avoid the development of a complete and active immune response. Since Bloom's first studies on immunotherapy to treat high grade gliomas in 1960, many attempts have been made from different medical specialties to use the immune system as a weapon against a great diversity of cancers. Main objective of this study is to outline the basic features of the immune response inside the Central Nervous System, the strategies employed by astrocytic tumours to evade body defences, and to provide an extended literature review on research on immunotherapy, especially concerning its patho-physiology and the clinical results achieved till date.

[Akinetic mutism related to hydrocephalus and cerebellar surgery treated with bromocriptine and ephedrine. A pathophysiological review]. / Mutismo acinético relacionado con hidrocefalia y cirugía cerebelosa tratado con bromocriptina y efedrina. Revisión fisiopatológica.

Akinetic mutism (AM) is a behavioral disorder characterized by impossibility to move or speak in awake patients. lt has been typically described as a transient disorder following posterior fossa tumour resection. Besides, AM may also appear after recurrent shunt failures in hydrocephalic patients, with no tendency towards improvement, either spontaneously or with shunt revisions. However successful treatment of this second type of AM has been achieved with bromocriptine. We present a patient who developed AM after a posterior fossa surgery complicated by ventriculitis and multiple hydrocephalic events. AM only improved with bromocriptine. We review AM pathophysiology. Although not well known, it appears to be quite different, depending on its cerebellar or hydrocephalic origin. Damage to dentate nucleus or its efferents (mainly of glutamate) should promote AM of cerebellar origin, while damage to paraventricular monoaminergic pathways could explain AM related to repeated shunt failures which has successful response to bromocriptine treatment. However, a more complete study of this disorder is required to ascertain its aetiology.

[Management of recurrent trigeminal neuralgia after failed microvascular decompression]. / Manejo de la recidiva de la neuralgia del trigémino tras descompresión microvascular.

OBJECTIVE: To evaluate the surgical management of patients with trigeminal neuralgia after failed microvascular decompression. PATIENTS AND METHODS: Between 1993 and 2002, exploration of the posterior fossa was performed in 60 patients with trigeminal neuralgia. Records were analyzed retrospectively for those patients who needed another surgical procedure due to recurrence of pain, describing which procedure was performed, postoperative results and complications, and also the intraoperative findings when posterior fossa reexploration was realized. RESULTS: Eighteen patients had trigeminal neuralgia recurrence requiring a new surgical intervention, that consisted in a fossa posterior reexploration in nine patients and percutaneous radiofrequency termal rhizotomy in the other nine patients. Among the repeat operations, there was negative exploration in 7 patients (77%), and a partial sensory rhizotomy was performed. Most of thermocoagulations (5/9) were performed in old patients or patients with anestesic contraindication for the fossa posterior reexploration. CONCLUSION: Fossa posterior reexploration is an effective and safe surgical attitude in the treatment of recurrent trigeminal neuralgia after failed microvascular decompression. Partial sensory rhizotomy is recommended when the reexploration is negative.

[Decompressive craniectomy in malignant infarction of the middle cerebral artery]. / Craniectomía descomprensiva en ictus isquémico maligno de arteria cerebral media.

INTRODUCTION: Medically managed malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. However, several studies report a 40-50% increase in survival rates when decompressive craniectomy is performed. We present our experience with such surgical treatment and a literature review. PATIENTS AND METHODS: Seven decompressive craniectomies were performed on five patients for spaceoccupying MCA infarctions. Age ranged from 33 to 57 years-old (three males and two females). Preoperative GCS score was 9-13. Cranial CT was performed within the first 12 hours. Intracranial pressure (ICP) was continuously measured in four patients. Two infarcts occurred in the dominant hemisphere and three in the non-dominant side. Wide fronto-parieto-temporal craniectomies were performed. The duramater was opened and a large heterologous dura graft was placed. RESULTS: Surgery was performed on the second day after the onset of symptoms (median: 47 hours). Preoperative ICP ranged from 27 to 50 mmHg (median: 30.5 mmHg), with immediate postoperative ICP under 15 mmHg in all patients. Two patients (both non-dominant side) survived with good (after reoperation) and excellent functional outcome. They remain stable after ten and five months of follow-up. Three patients died five, five and thirteen days after admission due to uncontrollable high ICP. In our experience, bone removal itself was more relevant than dural opening for ICP control. Initial wide craniectomies may spare reoperations. CONCLUSION: The significant mortality rate reduction, a wide therapeutic window (2-3 days) and a low incidence of intraoperative complications make decompressive craniectomy a relevant treatment in malignant cerebral MCA infarction.

[Ruptured aneurysms presenting with subdural hematoma: management without angiography]. / Hematomas subdurales de causa aneurismática: estrategia terapéutica sin angiografía diagnóstica.

INTRODUCTION: Ruptured aneurysms on rare occasions cause subdural hematomas as described in literature. Sudden deterioration and coma is a common feature in those patients and a emergent surgical attitude is prompt required, even without confirmation with angiography. CASE REPORTS: We described three cases with acute subdural hematomas and little or no subarachnoid hemorrhage caused by ruptured aneurisms who presented with rapid neurologic deterioration. Urgent craniotomy and evacuation of the hematoma was performed without previous angiography in the three patients. In two patients the aneurysm was found during surgical exploration and subsequently clipped; in the remaining patient the aneurysm was embolized postoperatively. CONCLUSIONS: The occurrence of a subdural hematoma caused by the rupture of an intracranial aneurysm must be suspected in spontaneous subdural hematomas, especially in association with disproportioned conscious deterioration. All the three patients we report debuted with sudden conscious deterioration. If a ruptured aneurysm causing subdural hematoma is suspected, early surgical intervention is required even if angiography is not available. Severe neurological deficit and uncal herniation might still be reversible if provided decompression can be carried out in promptly. Angiography availability should not postpone surgery. Aneurysm presence should be ruled out whether by surgical exploration or by delayed angiography. Posterior communicating aneurysm are related to formation of subdural hematoma.

Una causa excepcional de deterioro neurológico repentino y coma / An exceptional cause of sudden neurological deterioration and coma

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Tratamiento microquirúrgico de la neuralgia trigeminal en mayores de 70 años, estudio de eficacia y seguridad / Microsurgical treatment of trigeminal neuralgia in patients older than 70 years: An efficacy and safety study

Introducción: El incremento de la incidencia de la neuralgia del trigémino (NT) con la edad junto con el creciente envejecimiento poblacional obligan a valorar las opciones de tratamiento quirúrgico de la NT refractaria en pacientes mayores. Métodos: Se revisó retrospectivamente una serie consecutiva de pacientes mayores de 70 años con NT refractaria tratados mediante descompresión microvascular (DMV) entre 1997 y 2015. Los resultados según la escala de dolor facial del Barrow Neurological Institute (BNI score), así como las complicaciones quirúrgicas, se compararon con los de pacientes menores de 70 años operados durante el mismo período. Resultados: Fueron intervenidos 40 pacientes mayores de 70 años (media 74,8 años). A los 34 meses de seguimiento medio, el 73% de los pacientes presentaba ausencia completa del dolor sin medicación (BNI I) y el 85% tenía un control del dolor sin o con medicación (BNI I-III). Comparando con 85 pacientes menores de 70 años intervenidos en el mismo período no se demostró una asociación significativa entre la edad y la obtención de un control del dolor (BNI I-III), pero sí entre la edad mayor de 70 años y la desaparición del dolor (BNI I; p = 0,03). La estancia media en mayores de 70 años fue significativamente mayor (p = 0,04), aunque la tasa de complicaciones posquirúrgicas fue similar a la de los pacientes más jóvenes. Conclusiones: Las personas de edad avanzada con NT refractaria pueden beneficiarse de un tratamiento mediante DMV con una probabilidad de éxito y unos riesgos equiparables a los de personas más jóvenes (AU)

Introduction: The increasing incidence of trigeminal neuralgia (TN) with age together with population ageing call for reexamination of surgical treatment options for refractory TN in elderly patients. Methods: Retrospective review of a consecutive series of patients older than 70 who underwent microvascular decompression (MVD) for refractory TN between 1997 and 2015. Outcomes based on the Barrow Neurological Institute pain intensity score (BNI score) and surgical complications were compared to those of patients younger than 70 undergoing MVD in the same period. Results: Forty patients older than 70 (mean = 74.8 years) underwent interventions. At a mean follow-up time of 34 months, 73% of the patients presented complete absence of pain without medication (BNI I) and 85% had good pain control with or without medication (BNI I-III). A comparison of these patients with the 85 patients younger than 70 treated surgically during the same period did not find a significant association between age and achievement of pain control (BNI I-II). However, there was a significant association between age older than 70 and complete pain relief (BNI I; P=.03). The mean hospital stay in patients over 70 was also significantly longer (P=.04), although the postsurgical complication rate was similar to that in younger patients. Conclusions: Elderly patients with refractory TN may benefit from treatment with MVD and the probability of success and surgical risk are comparable to those in younger patients (AU)

Surgical activity by Spanish Residents in Neurosurgery under the Training Programme in place since 1984 and changes to be implemented under the New Training Programme.

The Spanish National Committee for Neurosurgery has recently approved a new training programme which will shortly replace the former programme, which dates from 1984. The object of this report was to evaluate training in neurosurgery in Spain under the extant programme as perceived by the residents themselves. Assessment of any educational shortcomings might help in designing and evaluating the new one. Secondary objects were to present and discuss the principal changes to be implemented by the new programme.A questionnaire was circulated to the entire population of Spanish neurosurgical residents nation-wide (N = 62) in 2000, and this was repeated using the same group in 2001 and 2002. Residents were to answer questions concerning their experience during the reporting year and the preceding years, the results compiling information for 1996 to 2002. The questionnaire covered 72 surgical procedures listed in ascending order of complexity, with a five-point scale of surgical responsibility for each type. Responses were received from 48 residents. Spanish residents appeared to uniformly fulfil the general requirements of the former programme. The main shortcomings identified were low levels of surgical activity for certain special operations, especially functional and skull base approaches, and the absence of a log book specific to neurosurgery. The new training programme developed by the Spanish National Committee for Neurosurgery has taken these shortcomings into consideration and has introduced major changes in order to ensure that training will be improved on an ongoing basis.

[Differences between young and elderly patients in a protocol for the diagnosis and follow-up of arterial hypertension] . / Diferencias entre pacientes jóvenes y ancianos en un protocolo de diagnóstico y seguimiento de hipertensión arterial.

OBJECTIVE: To determine possible differences between the control of hypertension in elderly patients and in young patients. DESIGN: Retrospective observation study of the differences between initial and final systolic and diastolic blood pressure, of their relationship to inclusion in medical treatment, and of the control obtained with different kinds of, and changes in, treatment, of drug association, periodic check-ups, vascular disease and risk factors. SETTING: The urban Azpilagaña Health District in Pamplona. PATIENTS: 389 hypertense patients were studied retrospectively: 196 of 70 or over and 193 between 45 and 60. MAIN RESULTS: More older patients were treated medically (91.8% vs 84.5%, p = 0.024), and received combined two-drug treatment (30.1% vs 19.7%, p < 0.001), although the young people received more than two hypertension drugs more often (11.4% vs 2.5%, p < 0.001). Final control (< 140/90) was achieved more often among young people (39.9% vs 26.5%, p = 0.005). In the older patients group initial higher diastolic pressure was related to final pressure control. More older patients had periodic check-ups at the health centre (73.3% vs 63.7%, p < 0.001), but this practice only improved relative control (< or = 140/90) in young people (p = 0.001). Older patients used more diuretics (p < 0.001) and less beta-blockers (p < 0.001), with no differences for other hypertension drugs. CONCLUSIONS: There are differences based on age in treatment and control of hypertension patients. Older patients with diastolic hypertension are controlled more easily. Altogether and in both groups analysed, the percentage of people with normal pressure after treatment was higher than in other studies.

Tratamiento del dolor neuropático por desaferentización mediante lesión DREZ, resultados a largo plaz / Treatment of neuropathic deafferentation pain using DREZ lesions; long-term results

Introducción: El dolor por desaferentización secundario a lesiones medulares, avulsión del plexo braquial y otras lesiones de nervios periféricos, es a menudo refractario a tratamientos convencionales. Este trabajo evalúa la eficacia a largo plazo de la cirugía de lesión DREZ (Dorsal Root Entry Zone) en diversos síndromes de dolor neuropático por desaferentización. Pacientes y métodos: Se presenta una serie de 18 pacientes con dolor refractario por desaferentización tratados mediante lesión DREZ con radiofrecuencia. La eficacia inmediata y a largo plazo se valoró mediante la escala visual analógica (EVA) preoperatoria y postoperatoria, la valoración subjetiva del paciente, la reincorporación laboral y la reducción de la medicación analgésica. Resultados: El dolor en la EVA disminuyó significativamente de 8,6 antes de la cirugía a 2,9 de media al alta (p<0,001). A largo plazo, con un seguimiento medio de 28 meses (6-108), el dolor se mantuvo en 4,7 en la EVA (p<0,002). El porcentaje de pacientes con un alivio moderado a excelente del dolor fue de 77% al alta y 68% a largo plazo. El 67% de los pacientes redujo la medicación analgésica y el 28% se reincorporó al trabajo. Los mejores resultados se obtuvieron en los pacientes con avulsión del plexo braquial con una mejoría significativa del dolor a largo plazo en todos los casos. Conclusiones: La lesión DREZ por radiofrecuencia es un tratamiento eficaz y seguro para el dolor neuropático refractario por desaferentización (AU)

Introduction: Deafferentation pain secondary to spinal cord injury, brachial plexus avulsion and other peripheral nerve injuries is often refractory to conventional treatments. This study evaluates the long-term efficacy of spinal DREZ (Dorsal Root Entry Zone) lesions for the treatment of neuropathic pain syndromes caused by deafferentation.Patients and methodsA series of 18 patients with refractory deafferentation pain treated with radiofrequency DREZ lesions is presented. The immediate and long-term efficacy was measured with the Visual Analogue Scale (VAS) before and after treatment, the patient's subjective evaluation, the percentage of patients returning to work and the reduction in pain medication. Results: Pain on the VAS significantly decreased from 8.6 preoperatively to 2.9 (p<.001) at discharge. Over the long-term, with a mean follow-up of 28 months (6-108) pain remained at 4.7 on the VAS (p<0.002). The percentage of patients with moderate to excellent pain relief was 77% at discharge and 68% at the last follow-up. Pain medication was reduced in 67% of the patients and 28% returned to work. The best results were obtained in patients with brachial plexus avulsion, with a significant long-term pain relief in all cases. Conclusions:Radiofrequency DREZ lesion is an effective and safe treatment for refractory neuropathic pain caused by deafferentation (AU)