RESUMEN
The brain of an 1 8q deletion/3p trisomy patient is described. The findings revealed septo-optic dysplasia, dentato-olivary dysplasia, deficiency of myelination and disordered neuronal migration. Many of these pathological changes overlap the findings previously described in 18q deletion. An understanding of the pathological changes in the brain of these individuals provides the basis for therapeutic management of their symptoms.
Asunto(s)
Anomalías Múltiples/patología , Encéfalo/anomalías , Deleción Cromosómica , Displasia Septo-Óptica/patología , Trisomía/patología , Anomalías Múltiples/genética , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 3 , Humanos , Lactante , MasculinoRESUMEN
Sodium borocaptate (BSH) and boronophenylalanine (BPA) are two drugs that have been used clinically for boron neutron capture therapy (BNCT) of brain tumors. We previously have reported that hyperosmotic mannitol-induced disruption of the blood-brain barrier (BBB-D), followed by intracarotid (i.c.) administration of BPA or BSH, either individually or in combination, significantly enhanced tumor boron delivery and the efficacy of BNCT in F98 glioma bearing rats. The purpose of the present study was to determine the short-term neuropathologic consequences of this treatment and the long-term effects on motor and cognitive function, as well as the neuropathologic sequelae 1 year following neutron capture irradiation. BBB-D was carried out in non-tumor bearing Fischer rats by infusing a 25% solution of mannitol i.c. followed by i.c. injection of BPA or BSH, either individually or in combination, immediately thereafter. Animals were euthanized 2 days after compound administration, and their brains were processed for neuropathologic examination, which revealed sporadic, mild, focal neuronal degeneration, hemorrhage, and necrosis. To assess the long-term effects of such treatment followed by neutron capture irradiation, non-tumor bearing rats were subjected to BBB-D after which they were injected i.c. with BPA (25 mg B/kg body weight (b.w)) or BSH (30 mg B/kg b.w.) either individually or in combination (BPA 12.5 mg and BSH 14 mg B/kg b.w.). Two and a half hours later they were irradiated at the Medical Research Reactor, Brookhaven National Laboratory, Upton, NY, with the same physical radiation doses (5.79, 8.10 or 10.06 Gy), delivered to the brain, as those that previously had been used for our therapy experiments. The animals tolerated this procedure well, after which they were returned to Columbus, Ohio where their clinical status was monitored weekly. After 1 year, motor function was assessed using a sensitive and reliable locomotor rating scale for open field testing in rats and cognitive function was evaluated by their performance in the Morris water maze, the results of which were similar to those obtained with age matched controls. After functional evaluation, the rats were euthanized, their brains were removed, and then processed for neuropathologic examination. Subtle histopathologic changes were seen in the choroid plexuses of irradiated animals that had received BPA, BSH or saline. Radiation related ocular changes consisting of keratitis, blepharitis, conjunctivitis and cataract formation were seen with similar frequency in most rats in each treatment group. Based on these observations, and the previously reported significant therapeutic gain associated with BBB-D and i.c. injection of BSH and BPA, the present observations establish its safety in rats and suggest that further studies in large animals and humans are warranted.
Asunto(s)
Barrera Hematoencefálica/efectos de la radiación , Borohidruros/toxicidad , Compuestos de Boro/toxicidad , Terapia por Captura de Neutrón de Boro , Encéfalo/patología , Cognición/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Neurotoxinas , Fenilalanina/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/toxicidad , Compuestos de Sulfhidrilo/toxicidad , Animales , Barrera Hematoencefálica/efectos de los fármacos , Borohidruros/administración & dosificación , Borohidruros/farmacocinética , Compuestos de Boro/administración & dosificación , Compuestos de Boro/farmacocinética , Encéfalo/efectos de los fármacos , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/radioterapia , Arteria Carótida Interna , Hemorragia Cerebral/patología , Ojo/efectos de los fármacos , Ojo/patología , Ojo/efectos de la radiación , Oftalmopatías/etiología , Oftalmopatías/patología , Inyecciones Intraarteriales , Masculino , Neutrones , Fenilalanina/administración & dosificación , Fenilalanina/farmacocinética , Fenilalanina/toxicidad , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Ratas , Ratas Endogámicas F344 , Compuestos de Sulfhidrilo/administración & dosificación , Compuestos de Sulfhidrilo/farmacocinética , Distribución TisularRESUMEN
OBJECTIVE: The purpose of this study was to obtain tumor and normal brain tissue biodistribution data and pharmacokinetic profiles for sodium borocaptate (Na2B12H11SH) (BSH), a drug that has been used clinically in Europe and Japan for boron neutron capture therapy of brain tumors. The study was performed with a group of 25 patients who had preoperative diagnoses of either glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) and were candidates for debulking surgery. Nineteen of these patients were subsequently shown to have histopathologically confirmed diagnoses of GBM or AA, and they constituted the study population. METHODS: BSH (non-10B-enriched) was infused intravenously, in a 1-hour period, at doses of 15, 25, and 50 mg boron/kg body weight (corresponding to 26.5, 44.1, and 88.2 mg BSH/kg body weight, respectively) to groups of 3, 3, and 13 patients, respectively. Multiple samples of tumor tissue, brain tissue around the tumors, and normal brain tissue were obtained at either 3 to 7 or 13 to 15 hours after infusion. Blood samples for pharmacokinetic studies were obtained at times up to 120 hours after termination of the infusion. Sixteen of the patients underwent surgery at the Beijing Neurosurgical Institute and three at The Ohio State University, where all tissue samples were subsequently analyzed for boron content by direct current plasma-atomic emission spectroscopy. RESULTS: Blood boron values peaked at the end of the infusion and then decreased triexponentially during the 120-hour sampling period. At 6 hours after termination of the infusion, these values had decreased to 20.8, 29.1, and 62.6 microg/ml for boron doses of 15, 25, and 50 mg/kg body weight, respectively. For a boron dose of 50 mg/kg body weight, the maximum (mean +/- standard deviation) solid tumor boron values at 3 to 7 hours after infusion were 17.1+/-5.8 and 17.3+/-10.1 microg/g for GBMs and AAs, respectively, and the mean tumor value averaged across all samples was 11.9 microg/g for both GBMs and AAs. In contrast, the mean normal brain tissue values, averaged across all samples, were 4.6+/-5.1 and 5.5+/-3.9 microg/g and the tumor/normal brain tissue ratios were3.8 and 3.2 for patients with GBMs and AAs, respectively. The large standard deviations indicated significant heterogeneity in uptake in both tumor and normal brain tissue. Regions histopathologically classified either as a mixture of tumor and normal brain tissue or as infiltrating tumor exhibited slightly lower boron concentrations than those designated as solid tumor. After a dose of 50 mg/kg body weight, boron concentrations in blood decreased from 104 microg/ml at 2 hours to 63 microg/ml at 6 hours and concentrations in skin and muscle were 43.1 and 39.2 microg/g, respectively, during the 3- to 7-hour sampling period. CONCLUSION: When tumor, blood, and normal tissue boron concentrations were taken into account, the most favorable tumor uptake data were obtained with a boron dose of 25 mg/kg body weight, 3 to 7 hours after termination of the infusion. Although blood boron levels were high, normal brain tissue boron levels were almost always lower than tumor levels. However, tumor boron concentrations were less than those necessary for boron neutron capture therapy, and there was significant intratumoral and interpatient variability in the uptake of BSH, which would make estimation of the radiation dose delivered to the tumor very difficult. It is unlikely that intravenous administration of a single dose of BSH would result in therapeutically useful levels of boron. However, combining BSH with boronophenylalanine, the other compound that has been used clinically, and optimizing their delivery could increase tumor boron uptake and potentially improve the efficacy of boron neutron capture therapy.
Asunto(s)
Astrocitoma/radioterapia , Borohidruros/farmacocinética , Terapia por Captura de Neutrón de Boro , Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Compuestos de Sulfhidrilo/farmacocinética , Adulto , Anciano , Astrocitoma/sangre , Astrocitoma/cirugía , Disponibilidad Biológica , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/cirugía , Terapia Combinada , Femenino , Glioblastoma/sangre , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Fantasmas de Imagen , Radiometría , Radioterapia Adyuvante , Distribución Tisular , Resultado del TratamientoRESUMEN
PURPOSE: Boronophenylalanine (BPA) and sodium borocaptate (Na(2)B(12)H(11)SH or BSH) have been used clinically for boron neutron capture therapy (BNCT) of high-grade gliomas. These drugs appear to concentrate in tumors by different mechanisms and may target different subpopulations of glioma cells. The purpose of the present study was to determine if the efficacy of BNCT could be further improved in F98-glioma-bearing rats by administering both boron compounds together and by improving their delivery by means of intracarotid (i.c.) injection with or without blood-brain barrier disruption (BBB-D). METHODS AND MATERIALS: For biodistribution studies, 10(5) F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Eleven to 13 days later animals were injected intravenously (i.v.) with BPA at doses of either 250 or 500 mg/kg body weight (b.w.) in combination with BSH at doses of either 30 or 60 mg/kg b.w. or i.c. with or without BBB-D, which was accomplished by i.c. infusion of a hyperosmotic (25%) solution of mannitol. For BNCT studies, 10(3) F98 glioma cells were implanted intracerebrally, and 14 days later animals were transported to the Brookhaven National Laboratory (BNL). They received BPA (250 mg/kg b.w.) in combination with BSH (30 mg/kg b.w. ) by i.v. or i.c. injection with or without BBB-D, and 2.5 hours later they were irradiated with a collimated beam of thermal neutrons at the BNL Medical Research Reactor. RESULTS: The mean tumor boron concentration +/- standard deviation (SD) at 2.5 hours after i. c. injection of BPA (250 mg/kg b.w.) and BSH (30 mg/kg b.w.) was 56. 3 +/- 37.8 microgram/g with BBB-D compared to 20.8 +/- 3.9 microgram/g without BBB-D and 11.2 +/- 1.8 microgram/g after i.v. injection. Doubling the dose of BPA and BSH produced a twofold increase in tumor boron concentrations, but also concomitant increases in normal brain and blood levels, which could have adverse effects. For this reason, the lower boron dose was selected for BNCT studies. The median survival time was 25 days for untreated control rats, 29 days for irradiated controls, 42 days for rats that received BPA and BSH i.v., 53 days following i.c. injection, and 72 days following i.c. injection + BBB-D with subsets of long-term survivors and/or cured animals in the latter two groups. No histopathologic evidence of residual tumor was seen in the brains of cured animals. CONCLUSIONS: The combination of BPA and BSH, administered i.c. with BBB-D, yielded a 25% cure rate for the heretofore incurable F98 rat glioma with minimal late radiation-induced brain damage. These results demonstrate that using a combination of boron agents and optimizing their delivery can dramatically improve the efficacy of BNCT in glioma-bearing rats.
Asunto(s)
Barrera Hematoencefálica , Borohidruros/administración & dosificación , Compuestos de Boro/administración & dosificación , Terapia por Captura de Neutrón de Boro/métodos , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Fenilalanina/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Compuestos de Sulfhidrilo/administración & dosificación , Animales , Borohidruros/farmacocinética , Compuestos de Boro/farmacocinética , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Ensayos de Selección de Medicamentos Antitumorales , Quimioterapia Combinada , Glioma/metabolismo , Glioma/mortalidad , Inyecciones Intraarteriales , Fenilalanina/administración & dosificación , Fenilalanina/farmacocinética , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Radiobiología , Dosificación Radioterapéutica , Ratas , Ratas Endogámicas F344 , Compuestos de Sulfhidrilo/farmacocinética , Factores de TiempoRESUMEN
Neutral glycolipid and ganglioside compositions were determined on 11 ependymal tumors, 12 medulloblastomas, 6 other neuronal tumors of the brain, 4 peripheral neuroblastomas, 1 cerebral primitive neuroectodermal tumor (PNET), and 1 PNET of the thoracic wall. Within the group of tumors that can demonstrate neuronal phenotypes, there was an association between the degree of neuronal differentiation usually demonstrated by these tumors and the proportions of both GD1a and 1b-pathway gangliosides. The amount of globoside also correlated with the amount of 1b pathway gangliosides. Patients with medulloblastomas whose 1b gangliosides made up over 15% of the total gangliosides survived longer that those with lower proportions of 1b gangliosides. The only gangliosides in the choroid plexus papilloma were GM3 and GD1a, but other ependymal tumors had significant amounts of GD1b and its metabolic precursors. Ependymoma and anaplastic ependymoma had similar neutral glycolipid compositions, which were different from subependymoma, which lacked ceramide monohexoside and ceramide dihexoside. These differences in glycolipid compositions suggest that there may be fundamental biological differences between these types of ependymal tumors.
Asunto(s)
Neoplasias Cerebelosas/patología , Epéndimo/patología , Gangliósidos/análisis , Glucolípidos/análisis , Meduloblastoma/patología , Adulto , Química Encefálica , Neoplasias Cerebelosas/química , Neoplasias Cerebelosas/mortalidad , Niño , Preescolar , Epéndimo/química , Femenino , Glioma/química , Glioma/patología , Humanos , Lactante , Masculino , Meduloblastoma/química , Meduloblastoma/mortalidad , Persona de Mediana Edad , Neuroblastoma/química , Neuroblastoma/patología , Neoplasias del Sistema Nervioso Periférico/química , Neoplasias del Sistema Nervioso Periférico/patología , Valor Predictivo de las Pruebas , Pronóstico , Análisis de SupervivenciaRESUMEN
We report on a C-to-T transition in exon 6 of the PLP gene in a male with Pelizaeus-Merzbacher disease/X-linked spastic paraplegia. The transition changes a glutamine at amino acid residue 233 to a termination codon. This premature stop codon probably results in a truncated protein that is not functional. Six other relatives were analyzed for the mutation and two female carriers were identified. Autopsy data on one male are presented.
Asunto(s)
Esclerosis Cerebral Difusa de Schilder/genética , Proteína Proteolipídica de la Mielina/genética , Paraplejía/genética , Mutación Puntual , Cromosoma X/genética , Adulto , Secuencia de Bases , Encéfalo/patología , Preescolar , Codón sin Sentido/genética , ADN/genética , Esclerosis Cerebral Difusa de Schilder/patología , Femenino , Ligamiento Genético , Humanos , Masculino , Paraplejía/patología , Linaje , Polimorfismo Conformacional Retorcido-Simple , Médula Espinal/patologíaRESUMEN
Lipoma of the internal auditory canal is a rare tumor that may be confused clinically with the much more common vestibular schwannoma. We present two cases of lipoma of the internal auditory canal. The clinical presentation is indistinguishable from that of vestibular schwannomas. The high signal intensity on T1-weighted magnetic resonance imaging, both with and without contrast, is consistent with other reports of lipoma. Review of the literature shows that lipomas of the internal auditory canal are histopathologically similar to lipomas of the cerebellopontine angle. The symptoms, erosive effect on the auditory canal, and gross appearance of this uncommon tumor are sometimes difficult to differentiate from those of a vestibular schwannoma. The diagnosis can be established by intraoperative examination of frozen sections.
Asunto(s)
Conducto Auditivo Externo/patología , Neoplasias del Oído/diagnóstico , Oído Interno/patología , Lipoma/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Audiometría/métodos , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neurilemoma/diagnóstico , Población BlancaRESUMEN
Mitochondrial myopathies are heterogeneous disorders. They may present at any age with a variable clinical course. We report a 6-year-old boy presenting as spastic cerebral palsy for 4 years, then athetotic movements and loss of milestones. He was eventually found to have NADH dehydrogenase deficiency.
Asunto(s)
Parálisis Cerebral/enzimología , Miopatías Mitocondriales/enzimología , NADPH Deshidrogenasa/deficiencia , Atetosis/enzimología , Atetosis/patología , Atetosis/fisiopatología , Ataxia Cerebelosa/enzimología , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Parálisis Cerebral/patología , Parálisis Cerebral/fisiopatología , Niño , Humanos , Masculino , Mitocondrias Musculares/enzimología , Miopatías Mitocondriales/patología , Miopatías Mitocondriales/fisiopatología , Destreza Motora/fisiología , Espasticidad Muscular/enzimología , Espasticidad Muscular/patología , Espasticidad Muscular/fisiopatología , Músculos/enzimología , Músculos/patologíaRESUMEN
We conducted a matched case-control study to investigate risk factors for the two most common types of brain tumors in children, astrocytic glioma and primitive neuroectodermal tumor (PNET). Since the study focused on gestational exposures, we restricted it to young children because these exposures would be expected to act early in life. Parents of 155 astrocytic glioma cases, 166 PNET cases, and controls identified by random digit dialing completed telephone interviews. Few associations occurred with the hypothesized risk factors, which were gestational exposure to alcohol, hair coloring products, farms, and substances containing N-nitroso compounds (passive smoking, makeup, incense, new cars, pacifiers, baby bottles, beer). Of the products studied that contain N-nitroso compounds, only beer was associated with a significantly increased risk of either tumor type [odds ratio (OR) for PNET = 4.0; 95% confidence interval (CI), 1.1-22.1; P = 0.04]. Elevated ORs for PNET were observed for farm residence of the mother during the pregnancy (OR = 3.7; 95% CI, 0.8-23.9; P = 0.06) and of the child for at least a year (OR = 5.0; 95% CI, 1.1-46.8; P = 0.04). Significant associations with astrocytoma were observed for mother's use of kerosene (OR = 8.9; 95% CI, 1.1-71.1; P = 0.04) and birth by Caesarean section (OR = 1.8; 95% CI, 1.1-3.2; P = 0.03). History of miscarriage was associated with a lower risk of PNET (OR = 0.5; 95% CI, 0.3-0.9; P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Astrocitoma/epidemiología , Neoplasias Encefálicas/epidemiología , Tumores Neuroectodérmicos Primitivos/epidemiología , Vigilancia de la Población , Efectos Tardíos de la Exposición Prenatal , Aborto Espontáneo/epidemiología , Factores de Edad , Agricultura , Consumo de Bebidas Alcohólicas/efectos adversos , Astrocitoma/etiología , Neoplasias Encefálicas/etiología , Canadá/epidemiología , Estudios de Casos y Controles , Cesárea/efectos adversos , Intervalos de Confianza , Femenino , Tinturas para el Cabello/efectos adversos , Humanos , Lactante , Recién Nacido , Queroseno/efectos adversos , Modelos Logísticos , Masculino , Análisis por Apareamiento , Tumores Neuroectodérmicos Primitivos/etiología , Compuestos Nitrosos/efectos adversos , Oportunidad Relativa , Embarazo , Características de la Residencia , Factores de Riesgo , Factores Socioeconómicos , Estados Unidos/epidemiologíaRESUMEN
N-nitroso compounds and their precursors, nitrites and nitrates, have been hypothesized as risk factors, and vitamins C and E, which inhibit N-nitroso formation, as protective factors for brain tumors. A case-control study of maternal diet during pregnancy and risk of astrocytoma, the most common childhood brain tumor, was conducted by the Childrens Cancer Group. The study included 155 cases under age six at diagnosis and the same number of matched controls selected by random-digit dialing. A trend was observed for consumption of cured meats, which contain preformed nitrosamines (a class of N-nitroso compounds) and their precursors (adjusted odds ratio [OR] for highest quartile of intake relative to lowest = 1.7, P trend = 0.10). However, no strong trends were observed for nitrosamine (OR = 0.8, P = 0.60); nitrite (OR = 1.3, P = 0.54); nitrate (OR = 0.7, P = 0.43); vitamin C (OR = 0.7, P = 0.37); or vitamin E (OR = 0.7, P = 0.48). Iron supplements were associated with a significant decrease in risk (OR = 0.5, 95 percent confidence interval = 0.3-0.8). The effect of several dietary factors differed by income level, making interpretation of the results difficult. Future research should investigate the effect of dietary components not assessed in this study, as these may explain the disparate effects by income level. The results of this study provide limited support for the nitrosamine hypothesis.
Asunto(s)
Astrocitoma/epidemiología , Neoplasias Encefálicas/epidemiología , Dieta , Embarazo , Canadá/epidemiología , Carotenoides/administración & dosificación , Preescolar , Femenino , Humanos , Renta , Hierro/administración & dosificación , Carne , Tumores Neuroectodérmicos Primitivos/epidemiología , Compuestos Nitrosos/administración & dosificación , Factores de Riesgo , Estados Unidos/epidemiología , Vitamina A/administración & dosificación , Vitamina E/administración & dosificación , beta CarotenoRESUMEN
Infantile acid maltase deficiency is an autosomal recessive disease that invariably leads to death in the first 2 years of life. Debrancher deficiency, also an autosomal recessive disease, however, carriers a slowly progressive course. We report a hypotonic infant with a typical clinical course of infantile acid maltase deficiency in whom biochemical investigation revealed complete deficiencies of both acid maltase and debrancher enzyme.
Asunto(s)
Glucano 1,4-alfa-Glucosidasa/deficiencia , Enfermedad del Almacenamiento de Glucógeno Tipo III/enzimología , Hipotonía Muscular/enzimología , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Electromiografía , Resultado Fatal , Glucano 1,4-alfa-Glucosidasa/genética , Enfermedad del Almacenamiento de Glucógeno Tipo III/genética , Humanos , Lactante , Masculino , Hipotonía Muscular/diagnóstico , Hipotonía Muscular/genéticaRESUMEN
The occurrence of cancer and neurological disorders in first- and second-degree relatives of children in the United States and Canada diagnosed with brain tumor before age six was investigated. A pair-matched case-control study with 155 astrocytoma and 166 primitive neuroectodermal tumor (PNET) cases was performed. Cases were identified through the Childrens Cancer Group. Controls were selected by random-digit dialing and matched to cases on age, race, and telephone area code and exchange. Childhood cancers were more common in PNET relatives compared with the general population (standardized incidence ratio [SIR] = 2.5, 95 percent confidence interval [CI] 1.1-4.8, P = 0.02) and with control relatives (odds ratio [OR] = 3.0, CI = 0.5-30, P = 0.29). For astrocytoma, nonsignificant excesses of brain tumor, leukemia/lymphoma, and childhood cancer occurred among case relatives compared with control relatives, but not compared with the general population. Astrocytoma cases were significantly more likely than controls to have a relative with seizures (OR = 2.5, CI = 1.2-4.9, P = 0.009), especially childhood seizures (OR = 3.4, CI = 1.2-12, P = 0.02), epilepsy (OR = 3.0, CI = 0.9-13, P = 0.08), and febrile convulsions (OR = 4.5, CI = 0.9-43, P = 0.07). A family history of stroke was not a risk factor for either type of brain tumor. These results suggest that some childhood brain tumors may result from a genetic susceptibility and that some risk factors may affect childhood astrocytoma and PNET differently.
Asunto(s)
Astrocitoma/epidemiología , Astrocitoma/genética , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/genética , Neoplasias/epidemiología , Neoplasias/genética , Tumores Neuroectodérmicos Primitivos/genética , Convulsiones/epidemiología , Convulsiones/genética , Adulto , Factores de Edad , Canadá/epidemiología , Estudios de Casos y Controles , Preescolar , Epilepsia/epidemiología , Salud de la Familia , Femenino , Humanos , Incidencia , Renta , Leucemia/epidemiología , Linfoma/epidemiología , Masculino , Tumores Neuroectodérmicos Primitivos/epidemiología , Factores de Riesgo , Sarcoma/epidemiología , Estados Unidos/epidemiologíaRESUMEN
We present an unusual patient with a medical history of a fibrosing pseudotumor of the left orbit that had been stable for 8 years who presented with acute anterior hypophyseal failure. During the next 10-month period, sequential magnetic resonance scans showed a rapid growth of a plaque-like sellar and parasellar mass extending into the right cavernous sinus, right Meckel's cave, along the dural surfaces of the clivus, dens, and body of the second cervical vertebra. A transsphenoidal biopsy revealed sphenoid and intrasellar pseudotumor that invaded the adenohypophysis and had microscopic features identical to those of the previously excised orbital pseudotumor. Rapid growth of the pseudotumor continued despite a course of radiotherapy. Palsies of cranial nerves V and VI and of the sensory root of the cranial nerve VII developed on the right side. Steroid therapy was associated with improvement of the cranial nerve palsies. This is the first report of the sellar fibrosing pseudotumor producing not only anterior hypophyseal failure, but also cranial nerve dysfunction secondary to plaque-like extension into the cavernous sinus, Meckel's cave, and cranial base dura. This intracranial plaque-like extension of a fibrous pseudotumor corresponds to a hypertrophic intracranial pachymeningitis, which is a rare, previously described phenomenon associated to the syndrome of multifocal fibrosclerosis.
Asunto(s)
Enfermedades de los Nervios Craneales/etiología , Hipopituitarismo/etiología , Seudotumor Orbitario/complicaciones , Parálisis/etiología , Biopsia , Enfermedades de los Nervios Craneales/patología , Enfermedades de los Nervios Craneales/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Hipopituitarismo/patología , Hipopituitarismo/cirugía , Imagen por Resonancia Magnética , Persona de Mediana Edad , Órbita/patología , Seudotumor Orbitario/patología , Seudotumor Orbitario/cirugía , Parálisis/patología , Parálisis/cirugía , Pruebas de Función Hipofisaria , Hipófisis/patología , Tomografía Computarizada por Rayos XAsunto(s)
Neoplasias del Plexo Coroideo/patología , Ploidias , Adolescente , Niño , Preescolar , Neoplasias del Plexo Coroideo/líquido cefalorraquídeo , Neoplasias del Plexo Coroideo/genética , ADN de Neoplasias/análisis , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Nefelometría y Turbidimetría/métodos , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Encefalopatías/patología , Enfermedades Desmielinizantes/patología , Anticonvulsivantes/uso terapéutico , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/cirugía , Encefalopatías/diagnóstico , Encefalopatías/cirugía , Niño , Enfermedades Desmielinizantes/diagnóstico , Enfermedades Desmielinizantes/cirugía , Diagnóstico Diferencial , Femenino , Hemiplejía/tratamiento farmacológico , Hemiplejía/etiología , Humanos , Esteroides/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
Diffuse angiomatosis of the extremities is a rare condition characterized by extensive or multifocal benign mass-forming vascular lesions involving multiple tissue planes; histologically, adipose and fibrous tissue are admixed with vascular elements that vary from capillary proliferations to large vessels that are often structurally abnormal. Although diffuse angiomatosis most likely represents a hamartomatous form of arteriovenous malformation, it behaves clinically as a benign but slowly progressive and unresectable neoplasm. We describe a case of diffuse angiomatosis of the lower extremity that presented clinically as a soft-tissue sarcoma.
Asunto(s)
Angiomatosis/diagnóstico , Pierna/irrigación sanguínea , Sarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/diagnóstico , Angiomatosis/patología , Diagnóstico Diferencial , Femenino , Humanos , Pierna/patología , Masculino , Persona de Mediana Edad , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1nth----[11B]----4He(alpha) + 7Li + 2.79 MeV). The F98 tumor is an anaplastic glioma of CD Fischer rat origin with an aggressive biological behavior similar to that of human glioblastoma multiforme. F98 cells were implanted intracerebrally into the caudate nuclei of Fischer rats. Seven to 12 days later the boron-10-enriched polyhedral borane, Na2B12H11SH, was administered intravenously at a dose of 50 mg/kg body weight at varying time intervals ranging from 3 to 23.5 hours before neutron irradiation. Pharmacokinetic studies revealed blood 10B values ranging from 0.33 to 10.5 micrograms/ml depending upon the time after administration, a T1/2 of 6.2 hours, normal brain 10B concentrations of 0.5 microgram/g, and tumor values ranging from 1.1 to 12.8 micrograms/g. No therapeutic gain was seen if the capture agent was given at 3 or 6 hours before irradiation with 4 x 10(12) n/cm2 (10 MW-min; 429 cGy). A 13.5-hour preirradiation interval resulted in a mean survival of 37.8 days (P less than 0.01), compared to 30.5 days (P less than 0.03) for irradiated controls and 22.1 days for untreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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Boro/uso terapéutico , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Neutrones , Animales , Boro/farmacocinética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Transferencia de Energía , Glioma/metabolismo , Glioma/patología , Isótopos , Radioterapia/métodos , Ratas , Ratas Endogámicas F344RESUMEN
Fifty-eight patients with high-grade astrocytoma were treated by members of the Childrens Cancer Study Group in a prospective randomized trial designed to study the effectiveness of chemotherapy as an adjuvant to standard surgical treatment and radiotherapy. Following surgical therapy, patients were assigned randomly to radiotherapy with or without chemotherapy consisting of chloroethyl-cyclohexyl nitrosourea, vincristine, and prednisone. Treatment with chemotherapy prolonged survival and event-free survival. Five-year event-free survival was 46% for patients in the radiotherapy and chemotherapy group, and 18% for patients in the radiotherapy-alone group. Five-year survival was similarly improved. The differences in outcome due to treatment were statistically significant after correcting for imbalances in important prognostic factors (event-free survival, p = 0.026; survival, p = 0.067). The presence of mitoses or necrosis in the tumor specimen was associated with poorer outcome. Patients whose initial surgery was limited to biopsy, and patients with basal ganglia lesions, also had significantly worse outcome. Chemotherapy administered at the time of recurrence in a small number of patients did not produce any long-term survivors. This study is to our knowledge the only randomized trial to investigate effectiveness of chemotherapy in the treatment of high-grade astrocytoma in children.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Adolescente , Adulto , Astrocitoma/radioterapia , Neoplasias Encefálicas/radioterapia , Niño , Preescolar , Ensayos Clínicos como Asunto , Terapia Combinada , Dexametasona/administración & dosificación , Glioblastoma/radioterapia , Humanos , Lomustina/administración & dosificación , Recurrencia Local de Neoplasia , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Distribución Aleatoria , Vincristina/administración & dosificaciónRESUMEN
Transverse scans of the spinal cord routinely demonstrate signal variations related to the internal anatomy of the cord that do not accurately conform to histologic cross sections. This study evaluates the MR appearance of the axial anatomy of the spinal cord and provides correlation to histologic sections as a means to understand this discordance so that disease can be recognized more readily. Short TR/TE spin-echo studies, cardiac-gated multiecho spin-echo studies, and gradient-refocused-echo studies of normal excised human spinal cords, a normal volunteer, and gelatin phantoms were obtained by using the same imaging parameters at 1.5 T. Imaging artifacts were further investigated by using both a 128 x 256 and 256 x 256 matrix with a varying phase-encoded axis. Histologic sections of the excised cords, which were stained for myelin, iron, and cell bodies (Nissl), were used for correlation to the images. We found that significant Fourier truncation and partial-volume imaging artifacts modulated the MR display of the cord. On short TR/TE images a ring of high signal at the periphery of the cord was due to a truncation artifact. The appearance of the central portions of the gray and white matter was affected variably by partial-volume averaging depending on the matrix size. White-matter tracts of the cord were always lower in signal than was the gray matter on all pulse sequences. This finding was not due to iron deposition or CSF motion artifacts. We suspect that this probably was related to dense, longitudinal organization of spinal tracts and resultant anisotropy of water molecule motion similar to that seen in the pyramidal tracts, tendons, and ligaments. We recommend the use of a 128 x 256 matrix with two averages (four excitations) when obtaining axial scans of the spinal cord in living subjects. Although truncation artifacts diminish image quality, the quality is superior to that of images obtained with a 256 x 256 matrix, in which longer scanning times result in motion artifacts and reduced signal to noise.