Paul Klimo

Subependymal Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex: Considerations for Surgical or Pharmacotherapeutic Intervention

Tuberous sclerosis complex is a genetic disorder caused by mutations in either the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple organ systems. Subependymal giant cell astrocytomas are slow-growing brain tumors associated primarily with tuberous sclerosis complex. They are usually located in the ventricles, often near the foramen of Monro, where they can cause an obstruction if they grow too large, leading to increased intracranial pressure. Surgery to remove a tumor has been the mainstay of treatment but can be associated with postoperative morbidity and mortality. Not all tumors and/or patients are suitable for surgery. The recent development of mammalian target of rapamycin inhibitors that target the pathway affected by TSC1/TSC2 mutations offers a novel pharmacotherapeutic option for these patients. We review the timing and use of surgery versus pharmacotherapy for the treatment of subependymal giant cell astrocytoma in patients with tuberous sclerosis complex.

A 2-Year-Old Girl with Dysmetria and Ataxia.

A 2-year-old girl presented with 1-month history of dysmetria and ataxia. Computer tomography (CT) of the brain showed a large parietal-occipital mass and marked hydrocephalus, for which she required placement of bilateral ventriculoperitoneal shunts. Magnetic resonance imaging (MRI) of the brain also revealed two nodules within the lateral ventricle (Figure 1A). Spine MRI showed abnormal leptomeningeal enhancement along the cervical spine, with additional enhancement in the thoracic and upper lumbar spine. A metastatic origin was excluded by exhaustive radiologic investigations, including body CT and positron emission tomography. Her disease progressed following completion of 6 months of intravenous and 3 months of oral chemotherapy; MRI showed interval increase in the size of the left temporal lobe ventricular lesions as well as worsening leptomeningeal disease and new parenchymal nodules. The tumor was completely excised. MICROSCOPIC PATHOLOGY

Isolated Optic Nerve Glioma in Children With and Without Neurofibromatosis: Retrospective Characterization and Analysis of Outcomes

Isolated optic nerve glioma is a rare tumor with no consensus for the best therapeutic approach. Therefore, tumor control and preservation of visual function remain a challenge. In this retrospective study, we describe our experience over 30 years in a single-institutional cohort of children with isolated optic nerve glioma, focusing on treatments and visual outcomes. Seventeen children were followed for a median period of 8 years (range, 2-22 years). Diagnosis was based on typical neuroradiologic findings, and 3 patients had histologic confirmation of their tumors. In our study, conservative management preserved the vision of most patients with neurofibromatosis type 1 (NF1). NF1-related optic nerve gliomas were less often treated but were associated with a lower probability of progression and with occasional spontaneous regression. Sporadic tumors more frequently exhibited aggressive clinical behavior with a higher propensity for posterior extension, often requiring surgical intervention.

Rapid and fulminant leptomeningeal spread following radiotherapy in diffuse intrinsic pontine glioma

A 4‐year‐old male presented with rapid‐onset cranial nerve palsy and ataxia. Brain magnetic resonance imaging (MRI) revealed a pontine mass lesion with discordant conventional and advanced imaging. A stereotactic core biopsy revealed glioblastoma with immunostaining suggestive of histone H3K27M and TP53 mutation, consistent with diffuse intrinsic pontine glioma. MRI 3 months after radiotherapy revealed extensive new leptomeningeal metastatic disease involving both the supra‐ and infratentorial brain, as well as the imaged portion of the spine. Tissue procured at the time of needle biopsy has undergone striking in vivo expansion as an orthotopic xenograft.