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Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in the middle temporal gyrus. However, we found interindividual variance in abundances and gene expression signatures, particularly in deep-layer glutamatergic neurons and microglia. A minority of donor variance is explainable by age, sex, ancestry, disease state, and cell state. Genomic variation was associated with expression of 150 to 250 genes for most cell types. This characterization of cellular variation provides a baseline for cell typing in health and disease.

Background: Low-grade gliomas (LGGs) comprise a diverse set of intrinsic brain tumors that correlate strongly with survival. Data on the effect of reoperation are sparse., Objective: To evaluate the effect of reoperation on patients with LGG., Methods: Fifty-two consecutive patients with reoperated LGGs treated at the University of Washington between 1986 and 2004 were identified and evaluated in a retrospective analysis., Results: The average overall survival (OS) for this cohort was 12.95 ± 0.96 years. The overall 10-year survival rate was 57%. The absence of any residual tumor at either the first or second operation was associated with significantly increased OS. Negative prognostic variables for OS included the use of upfront radiation and pathology at recurrence. The average overall progression-free survival to the first recurrence (PFS1) was 6.23 ± 0.51 years. Positive prognostic factors for improved PFS1 included the use of upfront radiation therapy. Variables not associated with differences in PFS1 included the use of upfront chemotherapy, enhancement, pathology, extent of resection, the presence of residual tumor, and Karnofsky Performance Scale score <80. The average overall progression-free survival to the second recurrence was 2.73 ± 0.39 years. Pathology at recurrence was associated with significant differences in progression-free survival to the second recurrence, as was extent of resection at time of first recurrence, and Karnofsky Performance Scale score <80., Conclusion: This is among the largest studies to assess variables associated with outcome in patients with reoperated LGG. Reresection appears to provide significant benefit, and extent of resection remains the strongest predictor of OS.

In the developing brain, neuronal differentiation is associated with permanent exit from the mitotic cycle. This raises the possibility that neuronal differentiation may suppress proliferative activity, even in neoplastic cells. As a first step towards understanding the relation between neuronal differentiation and mitotic cycling in brain tumours, we studied the expression of NeuN (a neuronal marker) and Ki-67 (a mitotic marker) by double-labelling immuno-fluorescence in 16 brain tumours with neuronal differentiation. The tumours included a series of 11 central neurocytomas, and five single cases of other tumour types. In the central neurocytomas, NeuN(+) cells had a 15-fold lower Ki-67 labelling index, on average, than did NeuN(-) cells (P < 0.01). In the other tumours (one extraventricular neurocytoma, one desmoplastic medulloblastoma, one olfactory neuroblastoma, one ganglioglioma and one anaplastic ganglioglioma), the Ki-67 labelling index was always at least fourfold lower in NeuN(+) cells than in NeuN(-) cells. These results indicate that neuronal differentiation is associated with a substantial decrease of proliferative activity in neoplastic cells of central neurocytomas, and suggest that the same may be true across diverse types of brain tumours. However, tumours with extensive neuronal differentiation may nevertheless have a high overall Ki-67 labelling index, if the mitotic activity of NeuN(-) cells is high. The correlation between NeuN expression and reduced mitotic activity in neurocytoma cells is consistent with the hypothesis that neuronal differentiation suppresses proliferation, but further studies will be necessary to determine causality and investigate underlying mechanisms.

A 24-year-old woman with bifrontal headaches was found to have a well-circumscribed lesion in the frontal lobe subcortical white matter. Microscopic examination showed clusters of small round cells separated by hypocellular neuropil-like areas, and a distinct border between tumor and surrounding white matter. Synaptophysin was diffusely positive in neuropil-like areas, and many tumor cells expressed NeuN. Based on these findings, a diagnosis of "extraventricular neurocytoma" was made. A double-label immunofluorescence stain was performed with NeuN and Ki-67 antibodies to determine if NeuN+ cells remained in the mitotic cycle. No colocalization of these markers was found, thus supporting the hypothesis that neuronal differentiation (as marked by NeuN expression) is incompatible with continued proliferation of tumor cells, as well as normal neurons.

The neurofibromatosis 1 (NF1) gene has been implicated in astrocyte growth regulation in several studies. To determine whether loss of NF1 expression is associated with progression towards malignancy in sporadic astrocytomas from individuals without NF1, twenty-eight fresh astrocytoma operative specimens (low and high grade tumors) and seven primary human astrocytoma cell lines were examined for NF1 mRNA and protein expression. In all astrocytomas examined, increased NF1 expression was observed in the tumors relative to normal resting astrocytes. This increased neurofibromin expression correlated with elevated levels of activated p21-ras measured in both the fresh tumor specimens and the primary cell lines. Furthermore, when levels of activated p21 ras were decreased in astrocytoma cells expressing the ras inhibitory Asn-17 dominant-negative mutant, levels of neurofibromin expression decreased. In addition, fibroblasts induced to express oncogenic activated p21-ras(val12) had increased expression of NF1. These results suggested that neurofibromin expression is increased in human astrocytic tumors as a result of positive feedback regulation by increased levels of activated p21-ras.

Eight myelodysplastic children developed isolated lateral ventriculomegaly following shunt insertion for progressive hydrocephalus after closure of a myelomeningocele. In all patients a low-pressure distal slit valve (Uni-shunt) system preceded development of an isolated contralateral ventricle. Six of 8 children required a second contralateral shunt for a symptomatic isolated ventricle. Magnetic resonance imaging demonstrated a collapsed ventricle ipsilateral to the shunt secondary to distortion of the foramen of Monro. This was clearly depicted using three-dimensional color reconstructions of the ventricular anatomy. Low-pressure distal slit valves should be avoided in myelodysplastic children to prevent postshunt ventricle isolation.

We present a case of a 17-year-old male with an unbiopsied brainstem glioma who developed drop metastases a few months following completion of hyperfractionated radiation therapy to the primary site. The literature is reviewed with reference to intraspinal metastases from brainstem gliomas.

A case report of a Sylvian fissure meningioma in a 4-year-old female is presented. Childhood meningiomas are discussed, and the literature is reviewed with respect to the location of the lesion in the Sylvian fissure. The role of radiotherapy following subtotal resection of meningiomas is also described.