[Chemosensitivity test on brain tumors]. / Ensayos de quimiosensibilidad en cultivos primarios de tumores cerebrales.

UNLABELLED: During last 50 years chemotherapy has played a very important part in the cancer treatment. However, success or failures of news drugs in one particular cancer its difficult to predict. In vitro chemosensitivity is an attractive method for knowing about responses of a tumor to ChT treatment and assess the best dose in the patient with cancer. OBJECTIVE: To know brain tumors sensitivity against antineoplastic drugs. METHODS: Five different drugs (carmustin, camptotecin, taxol, hydroxyurea and tamoxifen) were tested on short-term cultures from 7 patients with Glioblastoma multiforme, 15 patients with meningiomas and one patient with meduloblastoma. For testing chemosensitivity we used MTT assay, and we measured optic density by spectophotometry to 450 nm. RESULTS. A total of 49 measurement were done, getting 44 valid dose-result curves. For each drug we used from 10-2 M to 10-12 M gap, and IC50 result was representative of tumor sensitivity to the drug. CONCLUSION: our data support MTT assays like valid method for measuring in vitro chemosensitivity in brain tumors to news drugs.

[Allelic loss at 1p/19q analysis in brain tumors of glial lineage]. / Análisis de la presencia de mutaciones por pérdida de heterocigocidad de 1p/19q en tumores cerebrales de estirpe glial.

BACKGROUND: To analyze in cerebral tumors of neuroepithelial tissue 1p/19q codeletions by study of loss of heterozygosity (LOH). A first implied objective was to get ready this molecular thecnique. METHODS: We aimed to determine several deletions mapping 1p and 19q chromosomes, three allelic loss of 1p and two allelic loss of 19q, in patients with cerebral tumors which were operated in our Department from October 2004 until March 2006. We have detected in blood and tumoral DNA loss of heterozygosity assay for molecular detection using PCR and capillary array electrophoresis of five markers (D1S508, D1S2734, D1S199, D19S412 y D19S219). RESULTS: Were included in the first part of this study 45 sample of neuroepithelial tissue supratentorial tumors: 29 glioblastoma, 1 gliosarcoma, 7 diffuse astrocytoma grade II, 1 oligoastrocytoma, 3 oligodendroglioma, 1 anaplastic oligodendroglioma, 1 xanthoastrocytoma, 1 dysembryoplastic neuroepithelial tumour and 1 pilocytic astrocytoma. We considered deleted regions identified when allelic ratio (T1/T2)/( N1/N2) was lower than 0.8. 80% of oligodendroglial tumors, 14% glioblastoma and 14% of diffuse astrocytoma grade II. CONCLUSIONS: Evaluation of 1p/19q allelic status by LOH analysis may provide useful information for guiding clinical and therapeutical decisions with high succes ratio. These results shown why patients with 1p/19q codeletion survive longer, because adjuvant alkylants adds further improvements to standard, surgery and radiotherapy, treatments.

Análisis de la presencia de mutaciones por pérdida de heterocigocidad de 1p/19q en tumores cerebrales de estirpe glial / Allelic loss at 1p/19q analysis in brain tumors of glial lineage

Objetivos. Analizar en tumores cerebrales, fundamentalmente de estirpe neuro-epitelial, la existencia de mutaciones en los cromosomas 1p y 19q por la técnica de análisis de la pérdida de hetero cigocidad (LOH). Un primer objetivo implícito fue poner a punto la técnica del análisis. Método. Hemos investigado la existencia de mutaciones en 3 alelos seleccionados del cromosoma 1p y en 2alelos del 19q de distintos tumores cerebrales de estirpeglial intervenidos de manera consecutiva en nuestro Centro desde Octubre de 2004 a Marzo de 2006. La metodología empleada ha sido la detección en ADN tumoral de tejido en fresco y en sangre del paciente del marcaje por PCR de amplificados y electroforesis analizando la pérdida de heterocigocidad de microsatélites, repeticiones de dinucleótidos, situados en D1S508, D1S2734, D1S199, D19S412 y D19S219. Resultados. Hemos incluido en esta primera fase de estudio un total de 45 muestras de pacientes intervenidos de tumores cerebrales supratentoriales de estirpe neuroepitelial y que incluyen: 29 glioblastomas, 1 gliosarcoma,7 astrocitomas grado II, 1 oligoastrocitoma, 3 oligodendrogliomas, 1 oligodendroglioma anaplásico,1 xantoastrocitoma, 1 tumor neuroepitelial disembrioplásico y 1 astrocitoma pilocítico. La presencia de mutación la hemos considerado cuando el índicealélico T1/ T2 era inferior a 0.8.Nl/N2 Por estirpe histológica destaca la presencia de mutaciónen un 80% de tumores oligodendrogliales, 14% deglioblastomas y 14% de astrocitomas fibrilares grado II. Conclusiones. La técnica de análisis de LOH en1p/19q es factible de realizar en centros que dispongan de técnicas de estudios genético-moleculares, con un alto índice de fiabilidad. De su resultado se desprende qué pacientes se pueden beneficiar del tratamiento con alquilantes añadiendo, a la terapia quirúrgica y/oradio terápica en uso hasta la fecha, una posibilidad de tratamiento con alto porcentaje de respuestas

Background. To analyze in cerebral tumors of neuroepithelial tissue 1p/19q codeletions by study of loss of heterozygosity (LOH). A first implied objective was to get ready this molecular thecnique. Methods. We aimed to determine several deletion smapping 1p and 19q chromosomes, three allelic loss of1p and two allelic loss of 19q, in patients with cerebral tumors which were operated in our Deparment from October 2004 until March 2006. We have detected in blood and tumoral DNA loss of heterozygosity assay for molecular detection using PCR and capillary array electrophoresis of five markers (D1S508, D1S2734,D1S199, D19S412 y D19S219). Results. Were included in the first part of this study 45sample of neuroepithelial tissue supratentorial tumors:29 glioblastoma, 1 gliosarcoma, 7 diffuse astrocytomagrade II, 1 oligoastrocytoma, 3 oligodendroglioma, 1anaplastic oligodendroglioma, 1 xanthoastrocytoma, 1dysembryoplastic neuroepithelial tumour and 1 pilocyticastrocytoma. We considered deleted regions identified when allelic ratio T1/T2 was lower than 0.8. 80% of oligodendroglial tumors, 14% glioblastoma and14% of diffuse astrocytoma grade II. Conclusions. Evaluation of 1p/19q allelic status by LOH analysis may provide useful information for guiding clinical and therapeutical decisions with high succes ratio. These results shown why patients with1p/19q codeletion survive longer, because adjuvant alkylants adds further improvements to standard, surgery and radiotherapy, treatments

[The treatment of intradural arteriovenous fistulas in the spine: two case reports]. / Tratamiento de fístulas arteriovenosas intradurales dorsales medulares: presentación de dos casos.

INTRODUCTION: Spinal dural arteriovenous fistulas (AVFs) frequently cause progressive myelopathy. Although endovascular approaches to spinal cord vascular malformations become an important adjunct or primary treatment of theses disorders, surgery can be safely performing in some categories. CASE REPORTS: Two males patients presented with progressively myelopathy two months and three years before, were diagnosed by typical MRI findings and spinal selective arteriograms of dorsal AVFs with single feeder of Spetzler's modified classification of spinal cord vascular lesions. After an attempt of embolization following diagnostic angiography in first case, surgical approach for clipping the afferent single feeder was done for both. CONCLUSIONS: Early recognition by selective diagnostic spinal angiography in patients with slowly progressive and fluctuating myelopathy, allow us surgery as recommended treatment in AVFs, so can effect a better outcome and often reverse presenting neurologic deficits.

[Medulloblastoma presenting as an extra-axial tumor in the cerebellopontine angle]. / Meduloblastoma de presentación extra-axial en el ángulo pontocerebeloso.

Differences in the imaging characteristic of adult medulloblastomas have been reported, including involvement of lateral cerebellar hemispheres with an extra-axial appearance. We present a case report of this rare circumstance: a 40 year old man presented with a 3 weeks history of headache, morning vomiting and left hearing difficulties. Magnetic resonance imaging revealed a left cerebellopontine angle (CPA) tumor, like a well circumscribed homogeneously enhancing mass. Through a left suboccipital craniectomy the tumor was totally removed. It presented as a cerebellopontine angle tumor, like a meningioma, and not as an intra-axial tumor. Histological analysis revealed that the tumor was composed of densely packed with highly proliferative cells that produce a dense intercellular reticulin fiber network. Inmunohistochemical analysis showed positive expression to synaptophysin, specific neuronal enolase and cromogranin. Histological diagnosis was crucial to define it as a desmoplastic medulloblastoma the present case and to perform postoperative adjuvant therapy. Neurosurgeons should be aware of the possibility that a CPA tumor is of intraaxial origin, because this increase the variability on pathological diagnosis.

[Survival analysis following the addition of temozolomide to surgery and radiotherapy in patients with glioblastoma multiforme]. / Análisis de la supervivencia global al añadir temozolamida al tratamiento quirúrgico y radioterápico en pacientes con glioblastoma multiforme.

OBJECTIVES: To analyze the effect of different therapies -surgery, radiotherapy, and chemotherapy (temozolomide)- on the survival of various groups of patients with glioblastoma multiforme (GBM). METHOD: The overall survival of a total of 85 patients with histopathological diagnosis of GBM was analyzed (descriptive statistics, Kaplan-Meier). Patients were divided into 4 treatment groups: group 1 (n=12), untreated patients (" no treatment" option was chosen by the family); group 2 (n=22), patients undergoing surgery only (retrospective series from the 1980s); group 3 (n=24), patients undergoing surgery + standard radiotherapy (control group, partially effective treatment); group 4 (n=27), patients undergoing surgery + radiotherapy + chemotherapy (temozolomide [TMZ]) (current study group). RESULTS: Mean age (one-way ANOVA) showed no significant difference between the groups. Mean/median survival (weeks) was as follows: group 1, 18/16; group 2, 23/14; group 3, 48/42; group 4, 70/64. The Kaplan-Meier analysis yielded the following 50% survival cutoffs (weeks): group 1, 16.00; group 2, 14.29; group 3, 42.00; group 4, 64.43. This demonstrated a significant difference when radiotherapy (group 3) was added to surgery (group 2) or no treatment (group 1), and a significant difference (p < 0.001) in survival when TMZ (group 4) was added to the so far considered as being the standard treatment (group 3: surgery + radiotherapy). CONCLUSIONS: Surgery alone does not result in a higher survival rate for GBM patients. However, surgery allows to establish a histopathological diagnosis, to improve signs and symptoms which are attributable to intracranial hypertension or tumour topography, and to reduce the number of target cells for adjunctive therapies. Radiotherapy improves survival and TMZ chemotherapy that is given after radiotherapy adds further survival benefit for patients.

Intraorbital arteriovenous malformation: case report.

An intraorbital arteriovenous malformation became symptomatic without exophthalmos but with chemosis and bruit of the left eye. The patient underwent only surgical treatment. The orbital rim was removed through a fronto-orbital approach. The chemosis was corrected and postoperative magnetic resonance imaging and angiography confirmed complete removal of the malformation. Histopathological examination disclosed an arteriovenous malformation in the extrabulbar fatty tissue without invasion of the extraocular muscles or optic nerve. The differences between various types of intraorbital malformations are discussed.

[Calcification of the thoracic yellow ligament as a cause of myelopathy]. / Calcificación del ligamento amarillo torácico como causa de mielopatía.

INTRODUCTION: Ossified yellow ligaments are a rare cause of thoracic myelopathy, which has been reported mainly in Japanese patients. The lower thoracic spine is the most common site affected and symptomatic patients usually begin to develop spactic paraparesis in combination with reduced depth sensation. CLINICAL CASE: A 45 year old female that since 8 months presented progressive gait disturbance with paresthesias to both lower extremities. Neurologic examination revealed a spactic gait with exaggeration of lower extremities reflexes, positive bilateral Babinski sign and reduced depth sensation. The MRI revealed concentric narrowing of the spinal canal between D(8) to D(11) with spinal cord compression due to enlarged calcified yellow ligaments and hypertrophy of articular processes. A D(9)-D(10) laminectomy was performed, with removed of calcified yellow ligaments, and foraminotomy in affected levels. The postoperative follow up during 30 months has been uneventful. CONCLUSION: Calcified yellow ligaments are a poorly understood cause of thoracic myelopathy which should be treated as early as possible in symptomatic patients.

[Retropleural paraspinal approach in the treatment of anterolateral thoracic spinal diseases]. / Vía paraespinal retropleural en el tratamiento de la patología anterolateral de la columna torácica.

The personal experience in the treatment of the spinal and paraspinal thoracic pathology using the paraspinal retropleural approach is presented. A total of 18 patients with neoplastic, traumatic and discal lesions were operated on. Improvement of neurological disturbances and pain was noted in all patients. The surgical technique for spinal cord and root decompression and also for anterior and/or posterior stabilization of the spine is described. The paraspinal retropleural approach is compared with the anterior transthoracic approach. The advantages of the paraspinal retropleural approach are: low rate of complications; allows a very wide decompression of the neurological elements as well as an anterior and/or posterior stabilization of the spine by a single approach; and it can be easily tailored for each lesion. These advantages are enhanced in the management of lesions located in the upper thoracic or thoracocervical levels.

Calcificación del ligamento amarillo torácico como causa de mielopatía / Calcification of the thoracic yellow ligament as a cause of myelopathy

Introducción. Descrita sobre todo en la población japonesa, la calcificación del ligamento amarillo es una causa poco frecuente de mielopatía torácica. En los pacientes que presentan síntomas, éstos consisten en paraparesia espástica y trastornos de la sensibilidad profunda; los niveles torácicos inferiores son los más frecuentemente afectados. Caso clínico. Mujer de 45 años de edad que desde hacía ocho meses presentaba una inestabilidad en la marcha de carácter progresivo, y parestesias en ambos miembros inferiores que le dificultaban la deambulación. La exploración neurológica puso de manifiesto una marcha espástica, con hiperreflexia en miembros inferiores, signo de Babinski positivo bilateral y trastornos en la sensibilidad profunda. Los estudios de RM mostraron una estenosis concéntrica del canal raquídeo en los niveles D8 a D11 a expensas de la calcificación de los ligamentos amarillos, con hipertrofia de los articulares. En la intervención quirúrgica se practicó laminectomía en D9 y D10, resección de los ligamentos amarillos calcificados y foraminotomía en los niveles implicados. La evolución postoperatoria hasta la actualidad, a 30 meses de seguimiento, es favorable. Conclusiones. La mielopatía por calcificación de los ligamentos amarillos es una entidad a tener en cuenta, afecta sobre todo a la zona torácica y debe plantearse su tratamiento quirúrgico tan pronto como sea posible en los pacientes sintomáticos (AU)

Resultados del tratamiento quirúrgico en una cohorte de pacientes con patología lumbar degenerativa / Results of surgical treatment in a cohort of patients with degenerative lumbar pathology

Objetivos: Evaluar los resultados obtenidos durante 8 años consecutivos en la cirugía de raquis lumbar en un grupo de pacientes con patología lumbar degenerativa. Se analizan una serie de factores pre- y perioperatorios que pueden influir en el resultado al final del periodo de seguimiento. Material y método: Se incluyen un total de 196 pacientes, con un seguimiento clínico medio de 14,5 meses (mínimo de 3 meses en el 98,5 por ciento de los casos). Un 5,6 por ciento de los pacientes han sido reintervenidos quirúrgicamente. En 136 casos la clínica era de lumbociatalgia unilateral (grupo 1) y en los 60 restantes p redominaba clínica bilateral (grupo 2). El pronóstico clínico se evaluó según la escala de la Japanese Orthopedics Association (JOA), considerándose favorable cuando entre la valoración pre- y postoperatoria, al final del periodo de seguimiento, existía una diferencia de >3 puntos. Resultados: En el grupo 1 se obtuvieron resultados favorables en el 75,7 por ciento de los pacientes y en el grupo 2 en el 75,0 por ciento. En el análisis univariable se identifica a la larga duración preoperatoria de los síntomas como la variable que tiende a mostrar un valor pronóstico más desfavorable en el grupo 1, no mostrando relevancia la edad, sexo, valoración radiológica, nivel de afectación, valoración de riesgo anestésico o antecedentes personales en ninguno de los 2 grupos. No existe diferencia en el resultado global final entre los pacientes intervenidos por presentar clínica uni o bilateral. Conclusiones: La cirugía de raquis lumbar en nuestra serie se muestra como un procedimiento terapéutico que obtiene resultados satisfactorios para tres cuartas partes de los pacientes. No se han detectado variables pre- u operatorias que permitan identificar aquellos pacientes que tendrán mala evolución. Son necesarios estudios a largo plazo y el análisis de otras variables que nos permitan una más adecuada selección de los pacientes que van a ser sometidos a tratamiento quirúrgico (AU)

[Assessment of the degree of resection of high grade supratentorial gliomas with early postoperative magnetic resonance]. / Valoración del grado de resección de los gliomas supratentoriales de alto grado con resonancia magnética postoperatoria precoz.

UNLABELLED: In this paper we report the results of a prospective study in which we evaluate the degree of tumor removal of 25 supratentorial high grade gliomas by means of an MRI performed in the early postoperative period. In all cases, there was preoperative enhancement 8 patients had been previously operated on while the others had their first operation. In all cases the postoperative early MRI was performed within the first week and in 15 within the first 3 days. In order to evaluate the degree of tumor removal the presence or not of enhancement was considered and if it existed, classified as linear or nodular. RESULTS: To avoid postsurgical artifacts it is important to perform the MRI as soon as possible after surgery, especially within the first 3 days. Generally, linear enhancement disappeared on subsequent follow-up examinations, showing that it probably does no represent residual, tumor while nodular enhancement usually does. Survival with the high-grade tumors was slightly higher in the group without postoperative enhancement or linear one than in the group with nodular enhancement but the difference was not significant.

[Prognosis value of p53 gene and cellular proliferation factors in malignant supratentorial gliomas]. / Significación pronóstica de los factores de proliferación celular y del gen p53 en gliomas malignos supratentoriales del adulto.

OBJECT: The aim of this study was to investigate prognosis value of p53 oncosuppresor gene and labeling index by MIB-1 and PCNA monoclonal antibodies in malignant gliomas. METHODS AND RESULTS: We operated 60 patient with malignant glioma between July 1994 and August 1998. Forty-five cases had the histopathological diagnosis of Glioblastoma Multiforme and fifteen cases of anaplastic astrocytoma or olygoastrocytoma. Initially we compare MIB-1/PCNA labeling index in eighteen cases. Patients < 40 years old, short period of symptoms preoperatively, only one cerebral lobe localization, total surgical exeresis, Karnofsky index > 70 postoperatively, low labeling index (MIB < 8.6%), forward radiotherapy treatment and surgical re-operation, were identified like favourable outcome factors in the uninvariable analysis. However to the multivariable analysis, only had outcome significance: patients < 40 years old, low labeling index, Karnofsky index > 70 postoperatively and surgical reoperation. CONCLUSIONS: On the basis of the results of current analysis, moreover classical factors associated with better outcome, low labeling index to Glioblastoma Multiforme have been noted in patients with longer survival, and must be included to conventional histopathological studies.

[Neuro-radiological findings in probable moyamoya disease]. / Hallazgos neurorradiológicos en probable enfermedad de moyamoya.

INTRODUCTION: Unilateral moyamoya disease presents as unilateral stenosis or obstruction of the supraclinoid internal carotid artery, which causes cerebral hypoperfusion resulting in seizures or transitorial ischemic accidents (TIA). CLINICAL CASE: Atypical moyamoya disease was diagnosed as the cause of intraventricular hemorrhage in a 41 year-old-woman. The cerebral angiography, CT, MR and brain SPECT are reported. CONCLUSION: We discuss the clinic course and diagnostic techniques in this unilateral, atypical moyamoya disease and which steps are necessary toward an acceptable method for diagnosis and pursuit.