Antitumor Profile of Combined Matricaria recutita Flower Extract and 5-Fluorouracil Chemotherapy in Sarcoma 180 In Vivo Model.

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

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)

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.

[Supratentorial endodermal cyst. Case report]. / Quiste endodérmico supratentorial: caso clínico y revisión de la literatura.

Endodermal cysts (EC) of the central nervous system are very uncommon lesions predominantly located in the spinal canal. Although rare, intracranial EC have been mainly described in the posterior fossa, with the supratentorial location considered exceptional. Apart from the low frequency of these lesions, their pathoembriology still remais unknown. We report a patient with a huge frontal EC and review the literature. A 62-year-old man presented with abnormal behaviour, disorientation and decreased level of consciousness after moderate head injury. Initial cranial CT scan revealed a large cyst in the left frontal region with marked midline shift. Emergency puncture and decompression of the cyst demonstrated a milky fluid with high protein levels. Cranial MRI after patient improvement confirmed the existence of the cystic lesion with less mass effect. Delayed surgery was performed with craniotomy and total removal of the cyst. Pathological examination confirmed the presence of a typical EC. Patient made a complete recovery on follow-up with no recurrence on postoperative MRIs. Differential diagnosis of EC based on radiological data is quite difficult. As aggresive behaviour of this condition has been described following incomplete resections, the treatment of choice is a radical removal of the cyst in one or two stages depending on patient clinical condition.

Quiste endodérmico supratentorial, caso clínico y revisión de la literatura / Supratentorial endodermal cyst. Case report

Los quistes endodérmicos que afectan al sistema nervioso central son lesiones expansivas muy poco frecuentes que se sitúan con mayor frecuencia a nivel espinal. Existen poco casos de localización intracraneal descritos en la literatura, la mayoría de ellos en la fosa posterior. Su etiopatogenia permanece aún desconocida. Presentamos el caso de un varón de 62 años que debuta con un cuadro de desorientación y comportamiento desinhibido tras sufrir un traumatismo craneoencefálico como consecuencia de un accidente de trá- fico. En la TC craneal realizada de urgencia se objetiva una lesión quística frontal izquierda de gran tamaño con importante desplazamiento de línea media. Se punciona y evacua el contenido del quiste obteniéndose un líquido opalino rico en proteínas y elementos celulares no identificados. La RMN nos confirma los hallazgos radiológicos previos. El paciente es intervenido de forma reglada mediante craneotomía, evacuación completa del contenido y extirpación de las paredes de la lesión. El estudio anatomopatológico resulta ser compatible con el diagnóstico de quiste endodérmico. Se han descrito casos de evolución agresiva con diseminación y recidiva tras manipulación quirúrgica de la lesión; por lo tanto, el tratamiento debe consistir en la extirpación completa de la misma. Para ello será necesario realizar el diagnóstico diferencial con otras lesiones quísticas intracraneales con el fin de adecuar el tratamiento a cada caso (AU)

Endodermal cysts (EC) of the central nervous system are very uncommon lesions predominantly located in the spinal canal. Although rare, intracranial EC have been mainly described in the posterior fossa, with the supratentorial location considered exceptional. Apart from the low frequency of these lesions, their pathoembriology still remais unknown. We report a patient with a huge frontal EC and review the literature. A 62-year-old man presented with abnormal behaviour, disorientation and decreased level of consciousness after moderate head injury. Initial cranial CT scan revealed a large cyst in the left frontal region with marked midline shift. Emergency puncture and decompression of the cyst demonstrated a milky fluid with high protein levels. Cranial MRI after patient improvement confirmed the existence of the cystic lesion with less mass effect. Delayed surgery was performed with craniotomy and total removal of the cyst. Pathological examination confirmed the presence of a typical EC. Patient made a complete recovery on follow-up with no recurrence on postoperative MRIs. Differential diagnosis of EC based on radiological data is quite difficult. As aggresive behaviour of this condition has been described following incomplete resections, the treatment of choice is a radical removal of the cyst in one or two stages depending on patient clinical condition (AU)

CREB is a key regulator of striatal vulnerability in chemical and genetic models of Huntington's disease.

Evidence of dysregulation of the CREB/CRE transcriptional pathway in animal models of Huntington's disease (HD) suggests that strategies designed to augment CRE-mediated transcription may be of therapeutic value. Here, we investigated the consequences of CREB activation and repression in chemical and transgenic mouse models of HD. In the 3-nitropropionic acid (3-NP) model, CREB phospho-activation in the striatum was potently repressed within the neurotoxic "core" region prior to cell death. Conversely, marked expression of phospho-CREB, as well the CREB-regulated cytoprotective gene Bcl-2, was detected in the "penumbral" region. To examine potential contributory roles for the CREB/CRE transcriptional pathway in striatal degeneration, we used both CREB loss- (A-CREB) and gain- (VP16-CREB) of-function transgenic mouse strains. 3-NP-induced striatal lesion size and motor dysfunction were significantly increased in A-CREB mice compared to controls. Conversely, striatal damage and motor deficits were diminished in VP16-CREB mice. Furthermore, transgenic A-CREB significantly accelerated motor impairment in the YAC128 mouse model of HD. Together, these results indicate that CREB functionality is lost during the early stages of striatal cell stress and that the repression of CREB-mediated transcription contributes to the pathogenic process.

[Radiation-induced cranial tumors: clinical series and literature review]. / Tumores craneales radioinducidos: serie clínica y revisión de la literatura.

Radiation induced tumors are well-known but rare complications of radiotherapy. Meningiomas are the most common radiation-induced (RI) cranial tumors, followed by gliomas and sarcomas, while other tumors as haemangioblastomas remain extremely exceptional. We present 7 patients with RI brain tumors diagnosed and treated at our institution between 1990 and 2006. Retrospective review of their clinical charts is supplied. All patients were irradiated during childhood as a treatment for another disease, and fulfilled the criteria of RI neoplasia. Four patients developed meningiomas and three developed other tumors (one glioblastoma, one softtissue sarcoma and one hemangioblastoma). In all cases a complete surgical removal was achieved. Preoperative assessment based on MRI supplied the correct diagnosis in six patients. The most important risks factors described in the literature for developing RI tumors are the age at which radiotherapy was administered and the dose of radiation applied. Differential diagnosis of RI tumors includes any tumor appearing after radiotheraphy, especially recurrences of the primary disease, as RI neoplasias are a rare complication. Even in cases with complete surgical resection, prognosis of this clinical entity is basically related to the histology of the RI tumor.

Tumores craneales radioinducidos: serie clínica y revisión de la literatura / Radiation-induced cranial tumors: clinical series and literature review

La inducción de neoplasias constituye una complicaciónbien conocida, aunque poco frecuente, de la irradiacióncraneal. Los meningiomas son las neoplasiascraneales radioinducidas (RI) más frecuentes, seguidasde los gliomas y los sarcomas, siendo extremadamenteraros otros tipos tumorales tales como loshemangioblastomas.Presentamos 7 pacientes con tumores cranealessecundarios a radioterapia, diagnosticados en nuestrohospital entre los años 1990 y 2006. Se realizó unarevisión retrospectiva de sus datos clínicos. Todos lospacientes habían sido irradiados en la infancia comotratamiento de otra enfermedad, y cumplían los criteriosde neoplasia RI.Cuatro pacientes desarrollaron meningiomas, mientrasque los 3 restantes presentaron otros tumores (unglioblastomas multiforme, un hemangioblastoma y unosteosarcoma de partes blandas). En los siete casos selogró una resección quirúrgica completa. El diagnósticopreoperatorio basado en resonancia magnética (RM)coincidió con el diagnóstico histológico en seis casos.Los factores de riesgo más importantes para desarrollaruna neoplasia RI son, según la literatura, la edad enel momento de la irradiación y la dosis administrada.El diagnóstico diferencial de estas neoplasias se planteacon aquellas lesiones que aparezcan tras la irradiacióncraneal, especialmente las recidivas, ya que el desarrollo de neoplasias RI constituye una complicación muy poco frecuente. El pronóstico de esta enfermedad, incluso tras resecciones completas, depende del diagnóstico histológico del tumor RI

Induction of tumors are , although rare , known complicaciónbien of cranial irradiation . Meningiomas are the most common radiation cranial neoplasms (RI ), followed by gliomas and sarcomas , being extremely rare other tumor types such as hemangioblastomas . Present 7 patients with RI brain tumors diagnosed in our hospital between 1990 and 2006. Unarevisión retrospective of his clinical data was performed . All patients were irradiated in childhood for treatment of other diseases , and met the RI criteriosde neoplasia . Four patients developed meningiomas, while the remaining 3 had other tumors ( unglioblastomas multiforme , a hemangioblastoma and a soft tissue osteosarcoma ) . In all cases a complete surgical resection was achieved . Preoperative diagnosis based on magnetic resonance (MR ) coincided with the diagnosis in six cases. The most important risk factors for developing RI tumors are, in the literature, age at irradiation and the dose administered. The differential diagnosis of these neoplasms arise with those injuries that arise after cranial irradiation , especially recurrences , since the development of malignancies RI is a very rare complication . The prognosis of this disease , even after complete resection depends on the histologic diagnosis of tumor RI

[Familiar glioblastoma presenting as a true multicentric tumor: etiopathogenic and prognostic features]. / Glioblastoma familiar múltiple de aparición metácrona: implicaciones etiopatogénicas y pronósticas.

Familial glioblastoma multiforme is a rather uncommon entity, being in most cases associated to known genetic disorders (as Turcot syndrome, Li-Fraumeni syndrome, neurofibromatosis, etc.). However, familial gliomas have also been described, although less frequently, independently of these genetic syndromes showing some special features regarding its etiology and clinical manifestations. Less than 10% of gliomas may be considered as true multicentric tumours either synchronous or metachronous in clinical presentation. Metachronous glioblastomas have been associated to better prognosis in some studies, with genetic studies having found clear differences among the tumors within same patients. Familial glioblastoma with metachronous presentation is an exceptional disorder. These tumors show special therapeutic implications due to the limitations of radiotherapy once the patient has already irradiated. A variety of non-specific mutations have been found in these patients but true characterization of this disorder remains unclear and will be based on further genetic studies. We present a clinical report on a patient harbouring a familial and metachronous glioblastoma. The main aspects of this entity are reviewed.

Glioblastoma familiar múltiple de aparición metácrona: implicaciones etiopatogénicas y pronósticas / Familiar glioblastoma presentig as a true multicentric tumor: etiopathogenic and pronostic features

El Glioblastoma multiforme con agregación familiares poco frecuente, asociándose la mayor parte de los casos a síndromes genéticos conocidos (como el síndrome de Turcot, el síndrome de Li-Fraumeni, la neurofibromatosis, etc). Sin embargo, existenotros gliomas familiares no asociados a estos cuadros sindrómicos que, aunque menos frecuentes, han mostrado unas características etiológicas y clínicas diferentes a las de los gliomas esporádicos. Por otra parte, hasta un 10% de los gliomas se consideran verdaderamente multicéntricos, apareciendo de modo síncrono o metácrono. Los glioblastomas de aparición metácrona han mostrado en algunos estudios un mejor pronóstico, habiéndose encontrado trastornos genéticos diferentes en los tumores de un mismo paciente. Los gliomas familiares con presentación metácrona son excepcionales. Estos tumores presentan unas implicaciones terapéuticas especiales por la limitación del tratamiento radioterápico tras el tratamiento inicial. Aunque se han identificado mutaciones variadas en estos pacientes, la identificación precisa de dichos trastornos se basará en el estudio de su sustrato genético específico. Presentamos un caso clínico que combina ambas peculiaridades revisando las características de esta patología

Familial glioblastoma multiforme is a rather uncommonentity, being in most cases associated to known genetic disorders (as Turcot syndrome, Li-Fraumeni syndrome, neurofibromatosis, etc.). However, family algliomas have also been described, although less frequently, independently of these genetic syndromes showing some special features regarding its etiology and clinical manifestations. Less than 10% of gliomas may be considered as true multicentric tumours either synchronous ormetachronous in clinical presentation. Metachronous glioblastomas have been associated to better prognosis in some studies, with genetic studies having found clear differences among the tumors within same patients. Familial glioblastoma with metachronous presentation is an exceptional disorder. These tumors show special therapeutic implications due to the limitations of radiotherapy once the patient has already irradiated. A variety of non-specific mutations have been found in these patients but true characterization of this disorder remains unclear and will be based on further genetic studies. We present a clinical report on a patient harbouring a familial and metachronous glioblastoma. The main aspects of this entity are reviwed

[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.

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

El mutismo acinético (MA) es un trastorno del comportamiento, caracterizado por la incapacidad para moverse o hablar en pacientes despiertos. Típicamente ha sido descrito como una complicación transitoria de la cirugía de tumores de fosa posterior. Sin embargo, el MA también puede aparecer tras múltiples fallos valvulares en pacientes hidrocefálicos. En estos casos, el MA no mejora espontáneamente, ni con revisiones valvulares, pero puede responder al tratamiento con bromocriptina. Presentamos una paciente con MA tras una cirugía de fosa posterior, complicada por una ventriculitis con dilataciones ventriculares repetidas, que sólo mejoró con bromocriptina. Revisamos la fisiopatología del MA. Aunque ésta no sea bien conocida, parece que la afectación del núcleo dentado y de sus eferencias (principalmente de glutamato) sería responsable del MA de origen cerebeloso, mientras que la afectación de las vías monoaminérgicas paraventriculares explicaría el MA relacionado con dilataciones ventriculares repetidas y que responde al tratamiento con bromocriptina. Aun así, se requiere un estudio más profundo de esta patología para aclarar su etiología

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