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  • Journal of Neurosurgery: Spine x
  • By Author: Nakaji, Peter x
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Nicholas C. Bambakidis, Eric M. Horn, Peter Nakaji, Nicholas Theodore, Elizabeth Bless, Tammy Dellovade, Chiyuan Ma, Xukui Wang, Mark C. Preul, Stephen W. Coons, Robert F. Spetzler and Volker K. H. Sonntag

Object

Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration.

Methods

The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted.

Results

Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means ± SDs, 46.9 ± 12.9 vs 20.9 ± 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups.

Conclusions

An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

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Eric M. Horn, Peter Nakaji, Stephen W. Coons and Curtis A. Dickman

Spinal meningeal melanocytomas are rare lesions that are histologically benign and can behave aggressively, with local infiltration. The authors present their experience with intramedullary spinal cord melanocytomas consisting of 3 cases, which represents the second largest series in the literature. A retrospective chart review was performed following identification of all spinal melanocytomas treated at the author's institution, based on information obtained from a neuropathology database. The charts were reviewed for patient demographics, surgical procedure, clinical outcome, and long-term tumor progression. Three patients were identified in whom spinal melanocytoma had been diagnosed between 1989 and 2006. The patients' ages were 37, 37, and 48 years, and the location of their tumor was C1–3, T9–10, and T-12, respectively. All 3 had complete resection with no adjuvant radiotherapy during follow-up periods of 16, 38, and 185 months, respectively. One patient demonstrated a recurrence 29 months after resection and the other 2 patients have demonstrated asymptomatic recurrences on imaging studies obtained at 16 and 38 months following resection.

With these cases added to the available literature, the evidence strongly suggests that complete resection is the treatment of choice for spinal melanocytomas. Even with complete resection, recurrences are common and close follow-up is needed for the long term in these patients. Radiation therapy should be reserved for those cases in which complete resection is not possible or in which there is recurrence.