Russell R. Lonser
Debbie K. Song and Russell R. Lonser
Because of the multiplicity and saltatory growth pattern associated with central nervous system hemangioblastomas in von Hippel-Lindau (VHL) disease, resection of individual tumors is usually reserved until symptoms occur, to avoid unnecessary surgery over the lifetime of a patient. Brainstem hemangioblastomas in VHL typically cause lower cranial nerve dysfunction, long-tract signs, sensory impairment, and gait abnormalities. The authors report on a 16-year-old girl with VHL who presented with abnormal early satiety resulting in growth and developmental arrest associated with a growing obex hemangioblastoma. Tumor resection resulted in restoration of appetite, with rapid weight gain, growth in stature, and onset of menses. These findings indicate that caudal brainstem-mediated mechanisms have a profound effect on satiety. Moreover, brainstem hemangioblastomas may present with abnormalities in satiety and feeding that can be effectively reversed with resection.
Steven M. Sorscher
Russell R. Lonser, Ronald R. Buggage and Robert J. Weil
Marc R. Mayberg
Mark M. Souweidane
Joshua M. Ammerman, Russell R. Lonser and Edward H. Oldfield
Object. To overcome the limitations associated with surgical approaches that have been described for accessing intraparenchymal lesions of the anteromedial region of the superior cerebellum, the authors used a posterior subtemporal transtentorial approach to remove tumors in this region. In this paper they describe the surgical technique that they used as well as the operative findings and clinical outcomes observed in patients who underwent resection of tumors in the anteromedial superior cerebellum.
Methods. The consecutive patients with anteromedial superior cerebellar tumors who underwent resection performed using the posterior subtemporal transtentorial approach at the National Institutes of Health were included in this study. Clinical, neuroimaging, and operative results were analyzed.
Three patients (two men and one woman) with anteromedial superior cerebellar tumors (two hemangioblastomas and one pilocytic astrocytoma) underwent resection via this approach. All the tumors were larger than 3 cm in diameter (range 3.1–3.5 cm). This approach provided excellent surgical access and permitted complete tumor resection in each case. The patients remained neurologically unchanged compared with preoperative baseline findings at the last follow-up examination (conducted at 4, 18, and 42 months postoperatively). One patient displayed a mild transient confusion immediately after surgery, but it resolved within 6 days.
Conclusions. The posterior subtemporal transtentorial approach provides excellent access to the anteromedial superior cerebellar region. This approach permits resection of large lesions in this location, while avoiding many of the limitations associated with other approaches to this site.
Marsha J. Merrill, Nancy A. Edwards and Russell R. Lonser
Central nervous system hemangioblastomas are the most common manifestation of von Hippel-Lindau (VHL) disease, an autosomal dominant tumor suppressor syndrome that results in loss of VHL protein function and continuous upregulation of hypoxia-inducible factors. These tumors are composed of neoplastic stromal cells and abundant vasculature. Stromal cells express markers consistent with multipotent embryonically arrested hemangioblasts, which are precursors for hematopoietic and vascular lineages. Notch receptors are transmembrane signaling molecules that regulate multiple developmental processes including hematopoiesis and vasculogenesis. To investigate the importance of notch signaling in the development of VHL disease–associated CNS hemangioblastomas, the authors examined the presence of the four notch receptors and downstream notch effectors in this setting.
The authors used surgical specimens obtained from confirmed VHL-associated hemangioblastomas. Immunohistochemical analysis for the four notch receptors and the downstream effectors was performed on formalin-fixed paraffin-embedded sections. Western blot analysis for HES1 was performed on frozen specimens.
All four notch receptors are present in hemangioblastomas. NOTCH1 and NOTCH4 receptors were widely and prominently expressed in both the stromal and vascular cells, NOTCH2 receptor expression was limited to primarily stromal cells, and NOTCH3 receptor expression was limited to vascular cells. All 4 receptors displayed a nuclear presence. Immunohistochemical analysis also demonstrated that downstream notch effectors, HES1 and HES5, were uniformly expressed in tumor stromal and vascular cells, but HES3, HEY1, and HEY2 were not. Strong HES1 expression was confirmed by Western blot analysis.
The presence of all four notch receptors and downstream effector molecules suggests that the notch signaling pathway plays a critical role in the maintenance of the undifferentiated pluripotent phenotype of these tumors and in the associated vascular response. Moreover, the prominent expression of notch receptors in VHL-associated CNS hemangioblastomas reveals a new and possibly potent therapeutic target.