OBJECT Adjuvant radiation following epidural spinal cord decompression for tumor is a powerful tool used to achieve local disease control and preserve neurological function. To the authors' knowledge, only 1 published report addresses adjuvant stereotactic radiosurgery after this procedure, but that study used significantly lower doses than are currently prescribed. The authors review their experience using high-dose single-fraction radiosurgery as a postoperative adjuvant following surgical decompression and instrumentation to assess long-term local tumor control, morbidity, and survival. METHODS A retrospective chart review identified 21 patients treated with surgical decompression and instrumentation for high-grade, epidural, spinal cord compression from tumor, followed by single-fraction high-dose spinal radiosurgery (dose range 18-24 Gy, median 24 Gy). Spinal cord dose was limited to a cord maximal dose of 14 Gy. Tumor histologies, time between surgery and radiosurgery, time to local recurrence after radiosurgery as assessed by serial MR imaging, and time to death were determined. Competing risk analysis was used to evaluate these end points. RESULTS In this series, 20 tumors treated (95%) were considered highly radioresistant to conventional external beam radiation. The planning target volume received a high dose (24 Gy) in 16 patients (76.2%), and a low dose (18 or 21 Gy) in 5 patients (23.8%). During the study, 15 (72%) of 21 patients died, and in all cases death was due to systemic progression as opposed to local failure. The median overall survival after radiosurgery was 310 days (range 37 days to not reached). One patient (4.8%) underwent repeat surgery for local failure and 2 patients (9.5%) underwent spine surgery for other reasons. Local control was maintained after radiosurgery in 17 (81%) of 21 patients until death or most recent follow-up, with an estimated 1-year local failure risk of 9.5%. Of the failures, 3 of 4 were noted in patients receiving low-dose radiosurgery, equaling an overall failure rate of 60% (3 of 5 patients) and a 1-year local failure estimated risk of 20%. Those patients receiving adjuvant stereotactic radiosurgery with a high dose had a 93.8% overall local control rate (15 of 16 patients), with a 1-year estimated failure risk of 6.3%. Competing risk analysis showed this to be a significant difference between radiosurgical doses. One patient experienced a significant radiation-related complication; there were no wound-related issues after radiosurgery. CONCLUSIONS Spine radiosurgery after surgical decompression and instrumentation for tumor is a safe and effective technique that can achieve local tumor control until death in the vast majority of patients. In this series, those patients who received a higher radiosurgical dose had a significantly better local control rate.

Mutations in the L1 neural cell adhesion molecule, a transmembrane glycoprotein, cause a spectrum of congenital neurological syndromes, ranging from hydrocephalus to mental retardation. Many of these mutations are single amino acid changes that are distributed throughout the various domains of the protein. Defective herpes simplex virus vectors were used to express L1 protein with the clinical missense mutations R184Q and D598N in the Ig2 and Ig6 extracellular domains, respectively, and S1194L in the cytoplasmic domain. All three mutant proteins were expressed at similar levels in infected cells. Neurite outgrowth of cerebellar granule cells was stimulated on astrocytes expressing wild-type or S1194L L1, whereas those expressing R184Q and D598N L1 failed to increase neurite length. Live cell immunofluorescent staining of L1 demonstrated that most defective vector-infected cells did not express R184Q or D598N L1 on their cell surface. This greatly diminished cell-surface expression occurred in astrocytes, neurons, and non-neural cells. In contrast to wild-type or S1194L L1, the R184Q and D598N L1 proteins had altered apparent molecular weights and remained completely endoglycosidase H (endoH)-sensitive, suggesting incomplete post-translational processing. We propose that some missense mutations in human L1 impede correct protein trafficking, with functional consequences independent of protein activity. This provides a rationale for how expressed, full-length proteins with single amino acid changes could cause clinical phenotypes similar in severity to knock-out mutants.

Effective management of CVJ tumors using radiation and/or surgery results in significant pain and functional improvement in properly selected patients. Advanced surgical techniques and stereotactic radiation may improve outcomes with less morbidity.