ABSTRACT
INTRODUCTION: The management of recurrent ependymoma within the paediatric population remains a therapeutic challenge. The options available are varied and patients may have already received prior radio- or chemotherapy. As yet, no consensus exists regarding their optimal treatment. We review the literature and present our contemporary management strategies for this interesting group of patients. RESULTS AND DISCUSSION: Survival following recurrence is poor and those prognostic factors that predispose to recurrence include extent of surgical resection and the timing of administration of adjuvant therapy. The extent of resection at re-operation can confer a survival advantage, without a necessary increase in morbidity. Strategies aimed at improving surgical resection at first diagnosis include improving and centralising post-surgical radiological review, defining what are true residuals, and centralising surgical review of incompletely resected tumours. Re-irradiation can improve survival, and with the use of conformal radiation fields need not necessarily lead to neuropsychological damage. Cisplatin and etoposide remain the most effective chemotherapeutic agents to date and with an increase in the understanding of tumour biology this may improve further. Because of the complex nature of this group of patients, decisions regarding their management require the involvement of a paediatric neurosurgeon, paediatric neuro-oncologist and paediatric radiation oncologist.
Subject(s)
Ependymoma/therapy , Neoplasm Recurrence, Local/therapy , Brain Neoplasms/diagnosis , Brain Neoplasms/mortality , Brain Neoplasms/therapy , Child , Ependymoma/diagnosis , Ependymoma/mortality , Humans , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/mortality , Prognosis , Spinal Neoplasms/diagnosis , Spinal Neoplasms/mortality , Spinal Neoplasms/therapyABSTRACT
11beta-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert 11-keto derivatives. As 11beta-hydroxysteroid dehydrogenase type 2 is highly expressed in the developing brain, but not in the adult CNS, we hypothesized that it may represent a protective barrier to the deleterious actions of corticosteroids on proliferating cells. To test this hypothesis we have investigated the development and growth of the cerebellum in neonatal C57BL/6 mice and mice lacking 11beta-hydroxysteroid dehydrogenase type 2 (-/-). 11beta-Hydroxysteroid dehydrogenase type 2-/- mice had consistently lower body weight throughout the neonatal period, coupled with a smaller brain size although this was normalized when corrected for body weight. The cerebellar size was smaller in 11beta-hydroxysteroid dehydrogenase type 2-/- mice, due to decreases in size of both the molecular and internal granule layers. When exogenous corticosterone was administered to the pups between postnatal days 4 and 13, 11beta-hydroxysteroid dehydrogenase type 2(-/-) mice were more sensitive, showing further inhibition of cerebellar growth while the wildtype mice were not affected. Upon withdrawal of exogenous steroid, there was a rebound growth spurt so that at day 21 postnatally, the cerebellar size in 11beta-hydroxysteroid dehydrogenase type 2-/- mice was similar to untreated mice of the same genotype. Furthermore, 11beta-hydroxysteroid dehydrogenase type 2-/- mice had a delay in the attainment of neurodevelopmental landmarks such as negative geotaxis and eye opening. We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 2/physiology , Animals, Newborn/physiology , Cerebellum/physiology , Glucocorticoids/physiology , 11-beta-Hydroxysteroid Dehydrogenase Type 2/biosynthesis , 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics , Animals , Body Weight/physiology , Brain/enzymology , Brain/growth & development , Cell Proliferation , Cerebellum/growth & development , Cerebellum/pathology , Corticosterone/blood , Female , Glial Fibrillary Acidic Protein/biosynthesis , Immunohistochemistry , In Situ Hybridization , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Organ Size/physiology , Postural Balance/physiology , Reflex/physiologyABSTRACT
Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.
