Faculty Bibliography

BACKGROUND: Trigeminal neuralgia (TN) that recurs after surgery can be difficult to manage. OBJECTIVE: To define management outcomes in patients who underwent gamma knife stereotactic radiosurgery (GKSR) after failing 1 or more previous surgical procedures. METHODS: We retrospectively reviewed outcomes after GKSR in 193 patients with TN after failed surgery. The median patient age was 70 years (range, 26-93 years). Seventy-five patients had a single operation (microvascular decompression, n=40; glycerol rhizotomy, n=24; radiofrequency rhizotomy, n=11). One hundred eighteen patients underwent multiple operations before GKSR. Patients were evaluated up to 14 years after GKSR. RESULTS: After GKSR, 85% of patients achieved pain relief or improvement (Barrow Neurological Institute grade I-IIIb). Pain recurrence was observed in 73 of 168 patients 6 to 144 months after GKSR (median, 6 years). Factors associated with better long-term pain relief included no relief from the surgical procedure preceding GKSR, pain in a single branch, typical TN, and a single previous failed surgical procedure. Eighteen patients (9.3%) developed new or increased trigeminal sensory dysfunction, and 1 developed deafferentation pain. Patients who developed sensory loss after GKSR had better long-term pain control (Barrow Neurological Institute grade I-IIIb: 86% at 5 years). CONCLUSION: GKSR proved to be safe and moderately effective in the management of TN that recurs after surgery. Development of sensory loss may predict better long-term pain control. The best candidates for GKSR were patients with recurrence after a single failed previous operation and those with typical TN in a single trigeminal nerve distribution.

BACKGROUND: Cellular transplantation holds promise for the management of a variety of neurological disorders. However, there is great variability in cell type, preparation methods, and implantation technique, which are crucial to clinical outcomes. OBJECTIVE: We compared manual injection with automated injection using a prototype device to determine the possible value of a mechanized delivery system. METHODS: Neural progenitor cells and bone marrow stromal cells were injected using manual or automated methods. Consistency of injection volumes and cell number and viability were evaluated immediately or 1 day after injection. RESULTS: When cells were delivered as a series of 3 manual injections from the same syringe, the variation in fluid volume was greater than for single manual injections. Automated delivery of a series of 3 injections resulted in a lower variability in the amount of delivery than manual injection for both cell lines (1.2%-2.6% coefficient of variability for automated delivery vs 4.3%-24.0% for manual delivery). The amount delivered from injection 1 to injection 3 increased significantly with manual injections, whereas the amount injected did not vary over the 3 injections for the automated unit. Cell viability 1 day after injection was typically 30% to 40% of the value immediately after injection for the bone marrow stromal cells and 30% to 70% for the neural progenitor cells. There were no significant differences in viability attributed to the method of injection. CONCLUSION: The automated delivery device led to enhanced consistency of volumetric cell delivery but did not improve cell viability in the methods tested. Automated techniques could be useful in standardizing reproducible procedures for cell transplantation and improve both preclinical and clinical research.

OBJECT: The object of this study was to determine whether the radiation dose rate affects clinical outcomes in patients who undergo stereotactic Gamma Knife surgery (GKS) to manage typical trigeminal neuralgia (TN). METHODS: The authors retrospectively studied pain relief in 165 patients with medically intractable TN, who underwent 80-Gy GKS using a single 4-mm collimator between 1994 and 2005. No patient had received prior radiation treatment. The measured relative helmet output factor of the Gamma Knife was 0.8 throughout this interval, and the dose rate varied from 1.21 Gy/minute to 3.74 Gy/minute (median 2.06 Gy/minute). Irradiation time varied from 26.73 to 95.11 minutes. The authors divided patients into a low-dose-rate (LDR) group, in which the dose rate varied from 1.21 to 2.05 Gy/minute, and a high-dose-rate (HDR) group, in which the dose rate varied from 2.06 to 3.74 Gy/minute. Post-GKS, the patients' pain control was determined using the Barrow Neurological Institute (BNI) pain scale. There was no statistically significant difference between groups with respect to history of prior microvascular decompression (p = 0.410) or peripheral neuroablative procedures (p = 0.583). The length of symptoms in patients varied from 3 to 414 months with a median of 84 months (p = 0.698). Median follow-up was 26 months with a maximum of 139 months. RESULTS: Initial pain relief was obtained in 71% of patients in the LDR group and 78% in the HDR group (p = 0.547). Patients who initially obtained improved pain relief (BNI Scores I-IIIa) after GKS maintained pain control for median durations of 52 months (LDR group) and 54 months (HDR group) (p = 0.403). New or increased facial sensory dysfunction was found in 14.5% of patients in the LDR group and in 19.3% of patients in the HDR group (p = 0.479). CONCLUSIONS: The authors found that the GKS dose rate did not affect pain control or morbidity within the range of 1.21-3.74 Gy/minute. Cobalt 60 source decay did not affect outcomes of GKS for TN pain management, even for dose rates approximating a 2-half-life decay of the isotope.

BACKGROUND: Treatment options for dural arteriovenous fistulas (DAVFs) have expanded with the application of stereotactic radiosurgery (SRS). OBJECTIVE: To assess the role of SRS with or without embolization, we reviewed our entire DAVF experience. METHODS: Between 1991 and 2006, 40 patients with 44 DAVFs underwent Gamma knife SRS. Twenty-eight patients had upfront SRS before or after embolization and 12 patients underwent delayed SRS for recurrent or residual DAVFs after initial embolization. The median patient age was 60 years (range, 29-90). DAVFs were diagnosed in 7 patients after they sustained an intracranial hemorrhage. The median SRS target volume was 2.0 mL (range, 0.2-8.2 mL) and the median marginal dose was 21.0 Gy (range, 15-25 Gy). RESULTS: At a median follow-up of 45 months (range, 23-116 mo), a total of 28 patients (harboring 32 DAVFs) had obliteration confirmed by imaging. We found a 83% obliteration rate in patients who had upfront SRS with embolization and a 67% obliteration rate in patients who only had SRS. One patient died of an intracerebral hemorrhage 2 months after SRS. Cavernous carotid fistulas were associated with higher rates of occlusion (P = .012) and symptom improvement (P = .010) than were transverse-sigmoid sinus-related fistulas. CONCLUSION: When upfront SRS is possible in conjunction with embolization, successful DAVF obliteration is possible in most patients, especially those with carotid cavernous fistulas. SRS should target the entire fistula regardless of whether it precedes or follows embolization. In selected patients with a small-volume, low-risk DAVF, SRS alone is an effective treatment option in most patients.

OBJECT: To evaluate the role of stereotactic radiosurgery (SRS) in patients with recurrent or residual intracranial ependymomas after resection and fractionated radiation therapy (RT), the authors assessed overall survival, distant tumor relapse, progression-free survival (PFS), and complications. METHODS: The authors retrospectively reviewed the records of 21 children with ependymomas who underwent SRS for 32 tumors. There were 17 boys and 4 girls with a median age of 6.9 years (range 2.9-17.2 years) in the patient population. All patients underwent resection of an ependymoma followed by cranial or neuraxis (if spinal metastases was confirmed) RT. Eleven patients had adjuvant chemotherapy. Twelve patients had low-grade ependymomas (17 tumors), and 9 patients had anaplastic ependymomas (15 tumors). The median radiosurgical target volume was 2.2 cm(3) (range 0.1-21.4 cm(3)), and the median dose to the tumor margin was 15 Gy (range 9-22 Gy). RESULTS: Follow-up imaging demonstrated therapeutic control in 23 (72%) of 32 tumors at a mean follow-up period of 27.6 months (range 6.1-72.8 months). Progression-free survival after the initial SRS was 78.4%, 55.5%, and 41.6% at 1, 2, and 3 years, respectively. Factors associated with a longer PFS included patients without spinal metastases (p = 0.033) and tumor volumes < 2.2 cm(3) (median tumor volume 2.2 cm(3), p = 0.029). An interval >/= 18 months between RT and SRS was also associated with longer survival (p = 0.035). The distant tumor relapse rate despite RT and SRS was 33.6%, 41.0%, and 80.3% at 1, 2, and 3 years, respectively. Factors associated with a higher rate of distant tumor relapse included patients who had spinal metastases before RT (p = 0.037), a fourth ventricle tumor location (p = 0.002), and an RT to SRS interval < 18 months (p = 0.015). The median survival after SRS was 27.6 months (95% CI 19.33-35.87 months). Overall survival after SRS was 85.2%, 53.2%, and 23.0% at 1, 2, and 3 years, respectively. Adverse radiation effects developed in 2 patients (9.5%). CONCLUSIONS: Stereotactic radiosurgery offers an additional option beyond repeat surgery or RT in pediatric patients with residual or recurrent ependymomas after initial management. Patients with smaller-volume tumors and a later recurrence responded best to radiosurgery.

BACKGROUND: Intracerebral drug delivery using surgically placed microcatheters is a growing area of interest for potential treatment of a wide variety of neurological diseases, including tumors, neurodegenerative disorders, trauma, epilepsy, and stroke. Current catheter placement techniques are limited to straight trajectories. The development of an inexpensive system for flexible percutaneous intracranial navigation may be of significant clinical benefit. OBJECTIVE: Utilizing duty-cycled spinning of a flexible bevel-tipped needle, the authors devised and tested a means of achieving nonlinear trajectories for the navigation of catheters in the brain, which may be applicable to a wide variety of neurological diseases. METHODS: Exploiting the bending tendency of bevel-tipped needles due to their asymmetry, the authors devised and tested a means of generating curvilinear trajectories by spinning a needle with a variable duty cycle (ie, in on-off fashion). The technique can be performed using image guidance, and trajectories can be adjusted intraoperatively via joystick. Fifty-eight navigation trials were performed during cadaver testing to demonstrate the efficacy of the needle-steering system and to test its precision. RESULTS: The needle-steering system achieved a target acquisition error of 2 +/- 1 mm, while demonstrating the ability to reach multiple targets from one burr hole using trajectories of varying curvature. CONCLUSION: The accuracy of the needle-steering system was demonstrated in a cadaveric model. Future studies will determine the safety of the device in vivo.

PURPOSE: Hemorrhage from an arteriovenous malformation (AVM) is the commonest cause of childhood stroke. Management options for children include observation and medical management, surgical resection, endovascular embolization, or stereotactic radiosurgery, alone or in combination. METHODS: Radiosurgery is used for high-risk malformations in critical brain locations. While this goal is being achieved, there should be limited morbidity and hopefully no mortality from hemorrhage or radiation-induced brain injury. RESULTS: Physicians who consider AVM radiosurgery cite one or more of the following: (1) that radiosurgery is an effective therapy required for the management of deep-brain AVMs; (2) that radiosurgery is an effective therapy for residual AVMs after subtotal resection; (3) that radiosurgery is worthwhile in an attempt to lower management risks for AVMs in functional brain locations; (4) since embolization does not cure most AVMs, additional therapy such as radiosurgery may be required; and (5) microsurgical resection may not be the best choice for some children. CONCLUSION: Radiosurgery is the first and only biologic AVM therapy; it represents the beginnings of future cellular approaches to vascular malformation diseases. For this reason, the future of radiosurgery may be impacted positively by the development of other biologic strategies such as brain protection or endothelial sensitization.

PURPOSE: To analyze the outcomes of gamma knife stereotactic radiosurgery (SRS) for residual or recurrent craniopharyngiomas and evaluate the factors that optimized the tumor control rates. METHODS AND MATERIALS: A total of 46 patients with craniopharyngiomas underwent 51 SRS procedures at University of Pittsburgh between 1988 and 2007. The median tumor volume was 1.0 cm(3) (range, 0.07-8.0). The median prescription dose delivered to the tumor margin was 13.0 Gy (range, 9-20). The median maximal dose was 26.0 Gy (range, 20-50). The mean follow-up time was 62.2 months (range, 12-232). RESULTS: The overall survival rate after SRS was 97.1% at 5 years. The 3- and 5-year progression-free survival rates (solid tumor control) were both 91.6%. The overall local control rate (for both solid tumor and cyst control) was 91%, 81%, and 68% at 1, 3, and 5 years, respectively. No patients with normal pituitary function developed hypopopituitarism after SRS. Two patients developed homonymous hemianopsia owing to tumor progression after SRS. Among the factors examined, complete radiosurgical coverage was a significant favorable prognostic factor. CONCLUSION: SRS is a safe and effective minimally invasive option for the management of residual or recurrent craniopharyngiomas. Complete radiosurgical coverage of the tumor was associated with better tumor control.