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Russell R. Lonser

-enhanced delivery 2,13,14,16,18 von Hippel-Lindau disease Biology & treatment 9,15,17 Nervous system gene therapy First-in-man gene therapy studies for glioblastoma 5,22 Malignant glioma Biology, natural history, & treatment 1,3,10 IPSS = inferior petrosal sinus sampling. Ed also contributed to neurosurgical scientific advancement in other ways. He was President of the Society of Neurological Surgeons (SNS) (2008–2009) and Chair of the Scientific Advisory Board for the AANS Neurosurgical Research and Education Foundation (NREF) (2009–2012). He served on the Editorial Boards of

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Steven M. Sorscher

techniques are prolonging the survival of patients with these diseases, more cases of tumor-to-tumor metastases will likely be described for this and other syndromes involving multiple primary tumors. As Jarrell and colleagues discussed, hemangioblastomas may provide an ideal environment for tumor-to-tumor metastases given their vascularity. These lesions might also be referred to as “piebald” tumors, that is, neoplasms composed of varied components. Antiangiogenic therapy has already shown activity in hemangioblastomas and other VHL-associated tumors including

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Martin A. Baggenstos, John A. Butman, Edward H. Oldfield and Russell R. Lonser

✓Peritumoral cysts (those arising immediately adjacent to the tumor mass) are frequently associated with benign and malignant tumors of the brain and spinal cord (syringomyelia). The cystic component of central nervous system (CNS) tumors and associated peritumoral cysts are often the cause of clinical symptoms. Because of the common occurrence of peritumoral cysts with CNS neoplasms and the morbidity associated with them, advanced imaging, histological, and molecular techniques have been used to determine the mechanism underlying cyst formation and propagation. Based on evidence from such studies, edema appears to be a common precursor to peritumoral cyst formation in the CNS. Mediators of vascular permeability acting locally in the tumor and/or hydrodynamic forces within abnormal tumor vascula-ture appear to drive fluid extravasation. When these forces overcome the ability of surrounding tissue to resorb fluid, edema and subsequent cyst formation occur. These findings support the concept that the tumor itself is the source of the edema that precedes cyst formation and that resection of tumors or medical therapies directed at decreasing their vascular permeability will result in the resolution of edema and cysts.

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Russell R. Lonser, Ronald R. Buggage and Robert J. Weil

or posterior fossa venous thrombosis, although it did demonstrate leptomeningeal enhancement and cerebellar edema, causing fourth ventricular compression and tonsillar herniation ( Fig. 1 ). Despite high-dose corticosteroid therapy, a Cushing reflex acutely developed in the patient due to brainstem compression ( Fig. 1 ), with crescendo headaches, bradycardia, and systemic hypertension. An urgent suboccipital craniectomy with expansive duraplasty resulted in normalization of his blood pressure and heart rate. His initial recovery was uneventful, but 3 weeks

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Russell R. Lonser, John D. Heiss and Edward H. Oldfield

supplies both the lesion and normal neural tissue, devascularization of the tumor by direct perfusion with ETOH may be particularly useful. Likewise, patients who require immediate surgery that precludes preoperative embolic therapy should also be excellent candidates for direct injection of ETOH. Because absolute ETOH is neurotoxic, proper use requires that its contact with normal tissue be prevented. Placement of cotton patties over the surrounding tissue to protect it against inadvertent spills, taking measures to reduce leaking of ETOH along the needle path (small

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Russell R. Lonser, Lynnette Nieman and Edward H. Oldfield

hypercortisolemic. If IPSS is performed in the absence of sustained hypercortisolism, the normal corticotrophs are not suppressed and will respond to CRH. The resulting inferior petrosal sinus–to–peripheral ACTH gradient will suggest CD, regardless of the etiology of CS and in normal subjects. 80 , 112 Thus, during the eucortisolemic phase of cyclic CS or while under medical therapy to block cortisol production, false-positive results occur. The initial results of IPSS for the differential diagnosis of CS suggested that the diagnostic accuracy of IPSS was 100%. 34 , 75

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Mark M. Souweidane

In 2002 our laboratory published the first experience with using convection-enhanced delivery (CED) in the brainstem as a potential therapy for children with diffuse intrinsic pontine gliomas (DIPGs). 4 Since then, the strategy has been aggressively investigated and has recently been integrated into the clinical arena. There are 2 current clinical trials in the United States specifically designed for using CED in children with DIPG ( nos. NCT00880061 and NCT01502917). A major obstacle to the widespread implementation of CED for brain

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Marsha J. Merrill, Nancy A. Edwards and Russell R. Lonser

Several types of notch signaling inhibitors are currently available or in development. 3 , 33 , 41 Specifically, gamma secretase inhibitors prevent cleavage of the membrane-associated full-length notch, thereby preventing release of the intracellular signaling portion of the molecule. 33 This class of inhibitor has a well-tolerated clinical safety profile in other settings. 4 Other inhibitors interfere with notch ligand binding or with notch ICD transcription complex formation. 19 Notch inhibitors may have an advantage over existing therapies in that they can

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Russell R. Lonser, Malisa Sarntinoranont, Paul F. Morrison and Edward H. Oldfield

B ased on the rapid progression in understanding the precise pathobiology underlying various neurological diseases, a number of promising new putative therapeutics have been developed for specific disorders that have been ineffectually treated or are not currently treatable. While these agents have been successful in reversing disease-related pathology in vitro and/or in animal models, they have not been successfully translated into clinically effective therapies. One of the largest obstacles to the successful conversion of putative therapeutics into

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Marc R. Mayberg

transient vasodilation in affected arteries but hold some risk and are not suited for prolonged therapy or multiple vascular distributions. These limitations have led to the quest for a vasodilating agent for cerebral vasospasm that could be given orally or intravenously over a period of several days, was selective for cerebral arteries in spasm, and did not have untoward side effects. Oral nimodipine (a selective calcium channel blocker) proved effective in 4 prospective, randomized clinical trials 1 , 3 , 18–20 for preventing delayed ischemic deficits after SAH but