Faculty Bibliography

OBJECTIVE: To present a large series of patients and examine the learning curve of the endonasal endoscopic transplanum, transtuberculum approach for primarily suprasellar or sellar-suprasellar tumors.. METHODS: We identified 122 patients who underwent 126 surgeries using the transplanum, transtuberculum approach . Extent of resection was determined with volumetric analysis of MRI's. Results concerning vision, endocrine function and complications were noted. RESULTS: Average tumor volume was 14 cm3. The most frequent pathologies were pituitary macroadenoma (51.6%), craniopharyngioma (20.6%) and meningioma (15.9%). 73% presented with visual compromise. Rates of GTR and NTR for the group as a whole were 58.1% and 13.7%, and for the patients in whom GTR was intended (n=90), rates of GTR and NTR were 77.5% and 12.5% for a total of 90%. Extent of resection in this group was 97.6%. Vision improved in 52.4% and deteriorated in 4.8%. Favorable endocrine outcome occurred in 63.5%. CSF leak rate was 3.1% for the series as a whole. It improved from 6.3% in the first half of the series to 0% in the second half. Leak rates varied with technique from 11% (fat graft only) to 4.2% (gasket seal only) to 1.8% (fat plus nasoseptal flap) to 0% (gasket plus nasoseptal flap). The rate of other complications was 14.3% in the first half of the series and 1.6% in the second half. There was one infection (0.8%). CONCLUSION: The endonasal endoscopic transtuberculum transplanum approach is a safe and effective minimal access approach to midline pathology in the suprasellar cistern.

Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineage-tracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.

BACKGROUND: Spontaneous intracranial hypotension is an uncommon clinical entity. Heritable connective tissue disorders (HCTD), such as Marfan syndrome, are frequently implicated as an underlying cause, due to dural structural weaknesses that predispose patients to spontaneous cerebrospinal fluid (CSF) leak. Due to the high prevalence of multi-system disease in HCTD, diagnosis and treatment are often complicated. CASE DESCRIPTION: We present a 58-year-old female with Marfan syndrome on anticoagulation for a mechanical aortic valve replacement who came to medical attention with severe, acute-onset headache following a straining episode. Noninvasive magnetic resonance (MR) myelography confirmed thoracic CSF extravasations and multiple lumbar diverticula. The patient was treated conservatively and her symptoms resolved. CONCLUSION: We discuss the common presentation, diagnostic tools, and treatment options for spontaneous CSF leaks in patients with Marfan syndrome or related HCTD with an emphasis on noninvasive modalities and a review of the major radiographic criteria used to diagnose dural abnormalities, such as dural ectasia.

Glioblastoma multiforme (GBM) is a deadly primary brain malignancy. Glioblastoma stem cells (GSC), which have the ability to self-renew and differentiate into tumor lineages, are believed to cause tumor recurrence due to their resistance to current therapies. A subset of GSCs is marked by cell surface expression of CD133, a glycosylated pentaspan transmembrane protein. The study of CD133-expressing GSCs has been limited by the relative paucity of genetic tools that specifically target them. Here, we present CD133-LV, a lentiviral vector presenting a single chain antibody against CD133 on its envelope, as a vehicle for the selective transduction of CD133-expressing GSCs. We show that CD133-LV selectively transduces CD133+ human GSCs in dose-dependent manner and that transduced cells maintain their stem-like properties. The transduction efficiency of CD133-LV is reduced by an antibody that recognizes the same epitope on CD133 as the viral envelope and by shRNA-mediated knockdown of CD133. Conversely, the rate of transduction by CD133-LV is augmented by overexpression of CD133 in primary human GBM cultures. CD133-LV selectively transduces CD133-expressing cells in intracranial human GBM xenografts in NOD.SCID mice, but spares normal mouse brain tissue, neurons derived from human embryonic stem cells and primary human astrocytes. Our findings indicate that CD133-LV represents a novel tool for the selective genetic manipulation of CD133-expressing GSCs, and can be used to answer important questions about how these cells contribute to tumor biology and therapy resistance.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by heterotopic ossification of soft connective and muscle tissues, often as the result of minor trauma. The sequelae include joint fusion, accumulation of calcified foci within soft tissues, thoracic insufficiency syndrome, and progressive immobility. The authors report on a patient with FOP who developed severe spinal canal stenosis in the thoracic spine causing substantial myelopathy. He underwent a thoracic laminectomy and resection of a large posterior osteophyte. Unique considerations are required in treating patients with FOP, including steroid administration to prevent ossification and anesthetic technique. The nuances of neurosurgical and medical management as they pertain to this disease are discussed.

There has been increasing experience in the utilization of intraoperative magnetic resonance imaging (iMRI) for intracranial surgery. Despite this trend, only a few U.S centers have examined the use of this technology for transsphenoidal resection of tumors of the sella. We present the largest series in North America examining the role of iMRI for pituitary adenoma resection. We retrospectively reviewed our institutional experience of 59-patients who underwent transsphenoidal procedures for sellar and suprasellar tumors with iMRI guidance. Of these, 52 patients had a histological diagnosis of pituitary adenoma. The technical results of this subgroup were examined. A 1.5-T iMRI was integrated with the BrainLAB (Feldkirchen, Germany) neuronavigation system. The majority (94%) of tumors in our series were macroadenomas. Seventeen percent of tumors were confined to the sella, 49% had suprasellar extensions without involvement of the cavernous sinus, 34% had frank cavernous sinus invasion. All patients underwent at least one iMRI, and 19% required one or more additional sets of intraoperative imaging. In 58% of patients, iMRI led to the surgeon attempting more resection. A gross total resection was obtained in 67% of the patients with planned total resections. There was one case of permanent postoperative diabetes insipidus and no other instances of new hormone replacement. In summary, iMRI was most useful for tumors of the sella with and without suprasellar extension where the information from the iMRI extended the complete resection rate from 40 to 72% and 55 to 88%, respectively. As one would expect, it did not substantially increase the rate of resection of tumors with cavernous sinus invasion. Overall, iMRI was particularly useful in guiding resection safely, aiding in clinical decision making, and allowing identification and preservation of the pituitary stalk and normal pituitary gland. Limitations of the iMRI include a need for additional personnel and training as well as additional operative time, which diminishes over time as personnel learn to optimize workflow efficiency. Additional costs are mitigated in part by using the iMRI as an immediate postoperative scan. Other data emerging from our experience suggest that preservation of normal gland and thus avoidance of hypopituitarism may be improved by iMRI use, but longer follow-up periods are required to test this conclusion. iMRI can detect unsuspected complications sooner than routine postoperative imaging, potentially leading to improved outcomes. However, larger studies are needed.