Subependymal Giant Cell Astrocytoma

Abstract

Subependymal giant cell astrocytomas (SEGAs) are benign tumors (WHO grade I) that occur almost exclusively in the setting of tuberous sclerosis (TS), a well-defined, multi-system genetic syndrome. Most commonly originating from the region of the caudate nucleus, these tumors may cause obstruction of cerebrospinal fluid circulation leading to hydrocephalus. Less frequently, they may hemorrhage spontaneously, causing precipitous neurological impairment [1]. Mutations of the TSC-1 and TSC-2 genes, both effectors of the mTOR pathway (originally mammalian Target of Rapamycin, now formally mechanistic Target of Rapamycin), lead to the variably expressed systemic manifestations of TS; cardiac rhabdomyoma, renal angiolipomas, facial adenoma sebaceum, cortical tubers of the brain, and SEGAs. The standard treatment of symptomatic or enlarging SEGAs is surgical excision. Pharmacological effectors of the mTOR pathway, rapamycin (aka sirolimus) and its analogs have recently been shown to induce rapid involution of SEGAs; however, the optimal timing, dosage, safety, and duration of treatment remain areas of active clinical research. SEGAs in the context of TS represent an example of an emerging paradigm: targeted molecular-oncologic therapy.