Dirty-appearing white matter: a disregarded entity in multiple sclerosis.

Abstract

projecting in or outside of the fourth ventricle. Experiments have determined that the tumor progenitor cells in ependymoma correspond to RGCs. Transplantation of these RGClike cancer stem cells into the brains of rats produces ependymomas. It is also interesting to note that RGCs exposed to EMX2 give origin to supratentorial ependymoma in childhood but not in adults (EMX2 is a called a “negative regulator”). As neuroradiologists, we not uncommonly see protuberances of tissue of normal signal intensities along the walls of the lateral ventricles. These generally correspond to hyperplastic astrocytic polyps. Meddling with the function of EPHBEPHRIN in the SVZ interrupts neuroblast migration resulting in astrocytic proliferation and formation of polyps. What are the clinical implications of these discoveries? Normally, the human body defends its stem cells very well, so if brain tumors originate from these cells, it is safe to assume that the new lineages will be resistant to the damage induced by conventional radiation and chemotherapies. Emphasis is being placed on targeting the pathways that regulate the life cycles of cancer stem cells. For example, cells from ependymomas and certain leukemias produce a substance called -secretase, which is involved in aberrant cancer cell renewal via activation of NOTCH signaling. Inhibitors of this secretase are being tried in patients with leukemia and are being considered for treatment of children with advanced ependymoma within the US Pediatric Brain Tumor Consortium. Conventional therapies tend to kill normal and tumor cells but not the resistant brain tumor stem cells that eventually regenerate the tumor (this is the reason why glioblastomas always recur). In addition, the effect of conventional therapies on tumor cells is limited as they cannot effectively target all of the different cell lineages. It is clear what we have historically called ependymomas comprise at least 3 tumors that are developmentally and molecularly distinct, and new and different treatments will be needed for each subgroup. Similarly, glioblastomas and medulloblastomas comprise different subtypes that determine patients’ outcomes (at least 2 different glioblastoma subtypes are clearly recognizable). In the future, cultivation of individual brain tumor cells may lead to identification of specific molecular markers, which, in turn, may be used to prescribe personalized treatment protocols. Stem cells can also be engineered to produce substances (interleukins, metalloproteinases) that may induce tumor regression. Immortalized stem cells given through intravascular delivery migrate toward tumors. The use of stem cells as Trojan horses is currently experimental and it is possible that as they pass through the lung capillaries their migration towards the brain may be interrupted. This topic is of enormous complexity, and I have attempted to simplify it. I have based—and extensively quoted—most of the information expressed here on the 5 references cited below. Anyone who is interested in this topic is encouraged to read these articles.

DOI: 10.3174/ajnr.A1834

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@article{Filippi2010DirtyappearingWM, title={Dirty-appearing white matter: a disregarded entity in multiple sclerosis.}, author={Massimo Filippi and M . A . Rocca}, journal={AJNR. American journal of neuroradiology}, year={2010}, volume={31 3}, pages={390-1} }