De novo adamantinomatous craniopharyngioma with long-term pre-diagnostic imaging.

Adamantinomatous craniopharyngioma has a bimodal age distribution occurring in children aged 5-15 years and less frequently in adults aged 45-60 years. The current embryogenetic hypothesis suggests that adamantinomatous craniopharyngioma (ACP) arises from epithelial remnants of the craniopharyngeal duct or Rathke's pouch. It is thought that this tumor exists early on during childhood but remains indolent, growing very slowly until it is diagnosed incidentally or due to symptoms. Recent reports of de novo development of ACP, however, have challenged this theory. Herein, we present a case of an incidentally discovered de novo adamantinomatous craniopharyngioma that was documented to arise de novo on serial MRIs performed for a different indication. To our knowledge, this is the first report of a middle-aged patient who is diagnosed with a de novo ACP documented with contrast-enhanced MRIs of the sella over a 16-year period. This case challenges our current understanding of the pathophysiology of adamantinomatous craniopharyngioma.

Resting-State Functional Connectivity of the Middle Frontal Gyrus Can Predict Language Lateralization in Patients with Brain Tumors.

BACKGROUND AND PURPOSE: A recent study using task-based fMRI demonstrated that the middle frontal gyrus is comparable with Broca's area in its ability to determine language laterality using a measure of verbal fluency. This study investigated whether the middle frontal gyrus can be used as an indicator for language-hemispheric dominance in patients with brain tumors using task-free resting-state fMRI. We hypothesized that no significant difference in language lateralization would occur between the middle frontal gyrus and Broca area and that the middle frontal gyrus can serve as a simple and reliable means of measuring language laterality. MATERIALS AND METHODS: Using resting-state fMRI, we compared the middle frontal gyrus with the Broca area in 51 patients with glial neoplasms for voxel activation, the language laterality index, and the effect of tumor grade on the laterality index. The laterality index derived by resting-state fMRI and task-based fMRI was compared in a subset of 40 patients. RESULTS: Voxel activations in the left middle frontal gyrus and left Broca area were positively correlated (r = 0.47, P < .001). Positive correlations were seen between the laterality index of the Broca area and middle frontal gyrus regions (r = 0.56, P < .0005). Twenty-seven of 40 patients (67.5%) showed concordance of the laterality index based on the Broca area using resting-state fMRI and the laterality index based on a language task. Thirty of 40 patients (75%) showed concordance of the laterality index based on the middle frontal gyrus using resting-state fMRI and the laterality index based on a language task. CONCLUSIONS: The middle frontal gyrus is comparable with the Broca area in its ability to determine hemispheric dominance for language using resting-state fMRI. Our results suggest the addition of resting-state fMRI of the middle frontal gyrus to the list of noninvasive modalities that could be used in patients with gliomas to evaluate hemispheric dominance of language before tumor resection. In patients who cannot participate in traditional task-based fMRI, resting-state fMRI offers a task-free alternate to presurgically map the eloquent cortex.

Assessment of the language laterality index in patients with brain tumor using functional MR imaging: effects of thresholding, task selection, and prior surgery.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors. The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index (LI) for a group of controls, patients with tumor without prior surgery, and patients with tumor and prior surgery. MATERIALS AND METHODS: Seven controls, 9 patients with tumor without prior surgery, and 4 patients with tumor and prior surgery performed verb-generation, phonemic fluency, and semantic fluency language tasks during fMRI. Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs. LIs were compared within each group, between groups, and between language tasks. Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth. RESULTS: The language LI varied as a result of statistical thresholding, presence of tumor, prior surgery, and language task. Although patients and controls followed a similar shape in the LI curve, there was no optimal P value for determining the LI. Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold. Verb generation was the least variable task both between tasks and across groups. CONCLUSION: For preoperative patients with tumor, the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability. Our data suggest that the LI may be threshold- and task-dependent, particularly in the presence of adjacent tumor.

Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer.

Embryonic stem (ES) cells are fully pluripotent in that they can differentiate into all cell types, including gametes. We have derived 35 ES cell lines via nuclear transfer (ntES cell lines) from adult mouse somatic cells of inbred, hybrid, and mutant strains. ntES cells contributed to an extensive variety of cell types, including dopaminergic and serotonergic neurons in vitro and germ cells in vivo. Cloning by transfer of ntES cell nuclei could result in normal development of fertile adults. These studies demonstrate the full pluripotency of ntES cells.

Early cortical precursors do not undergo LIF-mediated astrocytic differentiation.

Multipotential stem cells have been isolated from the developing and adult CNS. Similar identified factors control the differentiation of these cells. A striking example is the instructive action of CNTF/LIF activating the JAK/STAT pathway to induce astrocytic differentiation in both fetal and adult CNS stem cells. Here we show that E12 cortical precursors express functional LIF receptors but do not exhibit this differentiation response to CNTF/LIF either in explant or in dissociated cell culture. The lack of response to LIF-induced astrocytic differentiation is maintained in cocultures with LIF responsive cells derived from E15 cortex. This suggests cell intrinsic differences between early and late stage precursors in the interpretation of LIF-mediated signaling; however, the early nestin-positive precursor population differentiates into both neurons and neural crest derivatives. These data define differences between CNS stem cells from different stages of cortical development. J. Neurosci. Res. 59:301-311, 2000. Published 2000 Wiley-Liss, Inc.

Concordance between functional magnetic resonance imaging and intraoperative language mapping.

Although the correspondence between functional-magnetic resonance imaging (fMRI) representations of the sensorimotor cortex and intraoperative electrophysiology (including somatosensory evoked potential, SSEP, recordings and direct cortical stimulation) has been reported, a similar correspondence between fMRI and intraoperative localization of the language-sensitive cortex is not as well established. The aim of the present study was to evaluate the concordance between fMRI and intraoperative electrophysiology with respect to the localization of the language-sensitive and sensorimotor cortices. We present the results of 21 patients who underwent language and sensorimotor mapping by fMRI and intraoperative electrophysiology including SSEP recordings (n = 21), direct cortical stimulation of motor cortex (n = 15) and direct cortical stimulation of Broca's and Wernicke's area (n = 5). When responses were obtained with both methods, localization of function concurred in all cases. These observations suggest that fMRI represents a reliable preoperative tool for the identification of language-sensitive areas.

Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats.

In vitro expansion of central nervous system (CNS) precursors might overcome the limited availability of dopaminergic neurons in transplantation for Parkinson's disease, but generating dopaminergic neurons from in vitro dividing precursors has proven difficult. Here a three-dimensional cell differentiation system was used to convert precursor cells derived from E12 rat ventral mesencephalon into dopaminergic neurons. We demonstrate that CNS precursor cell populations expanded in vitro can efficiently differentiate into dopaminergic neurons, survive intrastriatal transplantation and induce functional recovery in hemiparkinsonian rats. The numerical expansion of primary CNS precursor cells is a new approach that could improve both the ethical and the technical outlook for the use of human fetal tissue in clinical transplantation.