RESUMEN
BACKGROUND/AIMS: Large population-based studies are needed to assess the epidemiology and survival risk factors associated with pediatric brainstem gliomas. This retrospective study explores factors that may influence survival in this population. METHODS: Utilizing the SEER database, the authors retrospectively assessed survival in histologically confirmed brainstem gliomas in patients aged 17 and younger. Survival was described with Kaplan-Meyer curves and multivariate regression analysis. RESULTS: This analysis of 180 cases showed that age (hazard ratio [HR] 1.04, 95% CI 0.96-1.14, p = 0.34), non-white race (HR 1.00, 95% CI 0.35-2.85 p > 0.99), distant or invasive extension of the tumor (HR 0.4, 95% CI 0.08-2.53, p = 0.37), and radiation therapy (HR 1.27, 95% CI 0.52-3.11, p = 0.61) were not associated with decreased survival. High-grade tumor status (HR 8.64, 95% CI 3.49-21.41, p < 0.001) was associated with decreased survival. Partial resection (HR 0.11, 95% CI 0.04-0.30, p < 0.001) and gross-total resection (HR 0.03, 95% CI 0.01-0.14, p < 0.001) were associated with improved survival. CONCLUSIONS: High-grade brainstem gliomas have a worse prognosis. Early diagnosis and surgery appear to be associated with improved survival, while the role of radiation is unclear.
Asunto(s)
Astrocitoma/mortalidad , Neoplasias del Tronco Encefálico/mortalidad , Tronco Encefálico/cirugía , Glioma/mortalidad , Programa de VERF , Análisis de Supervivencia , Astrocitoma/patología , Astrocitoma/cirugía , Neoplasias del Tronco Encefálico/patología , Neoplasias del Tronco Encefálico/cirugía , Niño , Bases de Datos Factuales , Femenino , Glioma/patología , Glioma/cirugía , Humanos , Masculino , Pediatría , Estudios RetrospectivosRESUMEN
BACKGROUND AND IMPORTANCE: Moyamoya disease is a rare cerebrovascular disorder often treated by direct and indirect revascularization bypass techniques as a result of a typically devastating disease course and poor response to medical therapy. In this report, we describe the formation and subsequent management of a de novo arteriovenous fistula identified in the setting of a patient treated with direct bypass surgery, a previously unreported phenomenon. CLINICAL PRESENTATION: A 51-year-old woman presenting with Suzuki stage IV bilateral moyamoya disease underwent bilateral extracranial-to-intracranial superficial temporal artery-to-middle cerebral artery bypass without complication at our institution. At the 6-month follow-up, she demonstrated no evidence of residual neurological deficits or continued symptoms despite documentation of an arteriovenous fistula arising at the site of the right extracranial-to-intracranial bypass on routine follow-up cerebral angiography. CONCLUSION: We present the first reported case of de novo arteriovenous fistula formation after superficial temporal artery-to-middle cerebral artery bypass for the treatment of moyamoya disease. Treatment of such iatrogenic arteriovenous fistulae fed by a patent bypass vessel may prove challenging without associated compromise of the bypass, meriting careful evaluation of all potential therapeutic options. The fistula described herein most likely occurred secondary to recanalization of a previously thrombosed vein of Trolard. This case demonstrates the possibility of arteriovenous fistula formation as a potential sequela of revascularization bypass surgery and lends support to the previously described traumatic origin of fistula formation.
Asunto(s)
Fístula Arteriovenosa/etiología , Revascularización Cerebral/efectos adversos , Arteria Cerebral Media , Enfermedad de Moyamoya/cirugía , Arterias Temporales , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/terapia , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Exposure to neurotoxin aluminum neurotoxicity is accompanied by the perikaryal accumulation of tangles of phosphorylated neurofilaments (NFs). We examined their formation and reversibility under cell-free conditions. AlCl3 induced dose-dependent formation of NF aggregates, ultimately incorporating 100% of detectable NFs. The same concentration of CaCl2 induced approximately 25% of NFs to form longitudinal dimers and did not induce aggregation. AlCl3 induced similar percentages of aggregates in the presence or absence of CaCl2, and CaCl2 could not reduce pre-formed aggregates. CaCl(2)-induced dimers and AlCl(3)-induced aggregates were prevented by prior NF dephosphorylation. While CaCl(2)-induced dimers were dissociated by phosphatase treatment, AlCl(3)-induced aggregates were only reduced by approximately 50%, suggesting that aggregates may sequester phosphorylation sites. Since phosphatases regulate NF phosphorylation within perikarya, inhibition of NF dephosphorylation by aluminum would promote perikaryal NF phosphorylation and foster precocious phospho-dependent NF-NF associations. These findings are consistent with the notion that prolonged interactions induced among phospho-NFs by the trivalent aluminum impairs axonal transport and promotes perikaryal aggregation.
Asunto(s)
Aluminio/toxicidad , Ovillos Neurofibrilares/efectos de los fármacos , Proteínas de Neurofilamentos/efectos de los fármacos , Neuronas/efectos de los fármacos , Neurotoxinas/toxicidad , Cloruro de Aluminio , Compuestos de Aluminio/toxicidad , Animales , Transporte Axonal/efectos de los fármacos , Transporte Axonal/fisiología , Cloruro de Calcio/toxicidad , Cloruros/toxicidad , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Citoesqueleto/patología , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Proteínas de Neurofilamentos/química , Proteínas de Neurofilamentos/metabolismo , Neuronas/metabolismo , Neuronas/patología , Fosforilación/efectos de los fármacos , Estructura Terciaria de Proteína/efectos de los fármacos , Estructura Terciaria de Proteína/fisiologíaRESUMEN
The phosphorylation of neurofilaments (NFs) has long been considered to regulate their axonal transport rate and in doing so to provide stability to mature axons. Axons contain a centrally situated ;bundle' of closely opposed phospho-NFs that display a high degree of NF-NF associations and phospho-epitopes, surrounded by less phosphorylated ;individual' NFs that are often associated with kinesin and microtubules (MTs). Bundled NFs transport substantially slower than the surrounding individual NFs and might represent a resident population that stabilizes axons and undergoes replacement by individual NFs. To examine this possibility, fractions enriched in bundled NFs and individual NFs were generated from mice and NB2a/d1 cells by sedimentation of cytoskeletons over a sucrose cushion. More kinesin was recovered within individual versus bundled NF fractions. Individual but not bundled NFs aligned with purified MTs under cell-free conditions. The percentage of NFs that aligned with MTs was increased by the addition of kinesin, and inhibited by anti-kinesin antibodies. Bundles dissociated following incubation with EGTA or alkaline phosphatase, generating individual NFs that retained or were depleted of phospho-epitopes, respectively. These dissociated NFs aligned with MTs at a level identical to those originally isolated as individual NFs regardless of phosphorylation state. EGTA-mediated dissociation of bundles was prevented and reversed by excess Ca(2+), whereas individual NFs did not associate in the presence of excess Ca(2+). These findings confirm that bundling competes with NF-MT association, and provide a mechanism by which C-terminal NF phosphorylation might indirectly contribute to the observed slowing in axonal transport of phospho-NFs.
Asunto(s)
Cinesinas/metabolismo , Microtúbulos/metabolismo , Proteínas de Neurofilamentos/metabolismo , Animales , Línea Celular , Citoesqueleto/metabolismo , Femenino , Filamentos Intermedios/metabolismo , Masculino , Ratones , Fosforilación , Unión ProteicaRESUMEN
Neurofilament phosphorylation has long been considered to regulate their axonal transport rate, and in doing so it provides stability to mature axons. We evaluate the collective evidence to date regarding how neurofilament C-terminal phosphorylation may regulate axonal transport. We present a few suggestions for further experimentation in this area, and expand upon previous models for axonal NF dynamics. We present evidence that the NFs that display extended residence along axons are critically dependent upon the surrounding microtubules, and that simultaneous interaction with multiple microtubule motors provides the architectural force that regulates their distribution. Finally, we address how C-terminal phosphorylation is regionally and temporally regulated by a balance of kinase and phosphatase activities, and how misregulation of this balance might contribute to motor neuron disease.