Faculty Bibliography

OBJECT: The authors performed a retrospective review of prospectively collected data to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) for the treatment of patients harboring symptomatic solitary cavernous malformations (CMs) of the brainstem that bleed repeatedly and are high risk for resection. METHODS: Between 1988 and 2005, 68 patients (34 males and 34 females) with solitary, symptomatic CMs of the brainstem underwent Gamma Knife surgery. The mean patient age was 41.2 years, and all patients had suffered at least 2 symptomatic hemorrhages (range 2-12 events) before radiosurgery. Prior to SRS, 15 patients (22.1%) had undergone attempted resection. The mean volume of the malformation treated was 1.19 ml, and the mean prescribed marginal radiation dose was 16 Gy. RESULTS: The mean follow-up period was 5.2 years (range 0.6-12.4 years). The pre-SRS annual hemorrhage rate was 32.38%, or 125 hemorrhages, excluding the first hemorrhage, over a total of 386 patient-years. Following SRS, 11 hemorrhages were observed within the first 2 years of follow-up (8.22% annual hemorrhage rate) and 3 hemorrhages were observed in the period after the first 2 years of follow-up (1.37% annual hemorrhage rate). A significant reduction (p < 0.0001) in the risk of brainstem CM hemorrhages was observed following radiosurgical treatment, as well as in latency period of 2 years after SRS (p < 0.0447). Eight patients (11.8%) experienced new neurological deficits as a result of adverse radiation effects following SRS. CONCLUSIONS: The results of this study support a role for the use of SRS for symptomatic CMs of the brainstem, as it is relatively safe and appears to reduce rebleeding rates in this high-surgical-risk location.

OBJECT: Cell transplantation has shown promise for the treatment of various neurological disorders, but the factors that influence cell survival and integration following transplantation are poorly understood. In fact, little is known regarding how simple but potentially critical variables, including the method of cellular preparation and administration, might affect transplant success. The goal of the present study was to determine the impact of time between tissue preparation and implantation on cellular viability. Time can vary with cell preparation, delivery to the operating room, and surgical technique. This study was also designed to evaluate the sensitivity of various methods of assessing implant viability. METHODS: Cell lines of neural progenitor cells and bone marrow stromal cells were generated from healthy adult mice. On the day of experimentation, the cells were collected, suspended in a balanced salt solution, and sequentially assessed for viability for up to 3.5 hours based on their appearance under phase-contrast microscopy, their ability to retain a fluorescent dye, and their attachment to a cultivation surface for 24 hours. RESULTS: When viability was measured based on the ability of cells to retain a fluorescent dye, there was a decrease in viability of 10-15% each hour. Based on the ability of the cells to attach to a culture surface and grow for 24 hours, viability decreased more rapidly at approximately 20% per hour. In addition, only about one-third of the cells judged viable based on phase-contrast microscopy or acute dye retention were found to be viable based on plating, and only 10% of the cells initially judged as viable were still capable of survival after 3 hours in suspension. CONCLUSIONS: The authors' results indicate that that there can be significant losses in viability between preparation and implantation and that more sophisticated methods of evaluation, such as the ability of cells to attach to a substrate and grow, may be required to detect decreases in viability. The time between preparation and implantation will be an important factor in clinical trial design.

PURPOSE: We evaluated the role of Gamma Knife stereotactic radiosurgery in the multidisciplinary management of brain metastases from an undiagnosed primary cancer. METHODS AND MATERIALS: Twenty-nine patients who had solitary or multiple brain metastases without a detectable primary site underwent stereotactic radiosurgery between January 1990 and March 2007 at the University of Pittsburgh. The median patient age was 61.7 years (range, 37.9-78.7 years). The median target volume was 1.0 cc (range, 0.02-23.6 cc), and the median margin radiosurgical dose was 16 Gy (range, 20-70 Gy). RESULTS: After radiosurgery, the local tumor control rate was 88.5%. Twenty four patients died and 5 patients were living at the time of this analysis. The overall median survival was 12 months. Actuarial survival rates from stereotactic radiosurgery at 1 and 2 years were 57.2% and 36.8%, respectively. Factors associated with poor progression-free survival included large tumor volume (3 cc or more) and brainstem tumor location. CONCLUSIONS: Radiosurgery is an effective and safe minimally invasive option for patients with brain metastases from an unknown primary site.

PURPOSE: This study evaluated the role of radiosurgery in the management of symptomatic patients with brainstem compression from benign basal tumors. METHODS AND MATERIALS: Over a 17-year, period 246 patients (202 vestibular schwannomas and 44 meningiomas) with brainstem compression from benign skull-base tumors were managed with Gamma Knife radiosurgery. Median tumor volumes were 3.9 cm(3) (range, 0.8-39.0 mL) and 6.6 mL (range, 1.6-25.1 mL) for vestibular schwannomas and meningiomas, respectively. For both tumors, a median marginal dose of 13 Gy was prescribed. Median follow-up of patients was 65 months for vestibular schwannomas and 60 months for meningiomas. Patients were categorized into four groups on the basis of the tumor-brainstem relationship on neuroimaging. RESULTS: Preservation of function was stratified according to grade of brainstem compression. We analyzed the effect of radiosurgery on symptoms of brainstem compression. The tumor control rate was 100 % for meningioma and 97% for vestibular schwannomas (although 5% required an additional procedure such as a ventriculoperitoneal shunt). In patients with vestibular schwannoma, serviceable hearing was preserved in 72.0%. Balance improved in 31.9%, remained unchanged in 56.5%, and deteriorated in 11.6% of patients who had imbalance at presentation. Balance improved significantly in patients who had less tumor compression (p = 0.0357) after radiosurgery. Symptoms improved in 43.2% of patients with meningioma. CONCLUSION: Radiosurgery is a minimally invasive option for patients with benign basal tumors that indent or distort the brainstem. A high tumor growth control rate and satisfactory rate of neurological preservation and symptom control can be obtained with radiosurgery.

OBJECT: A retrospective study was conducted to reassess the benefit and safety of stereotactic radiosurgery (SRS) in patients with solitary cerebral cavernous malformations (CCMs) that bleed repeatedly and are poor candidates for surgical removal. METHODS: Between 1988 and 2005 at the University of Pittsburgh, the authors performed SRS in 103 evaluable patients (57 males and 46 females) with solitary symptomatic CCMs. The mean patient age was 39.3 years. Ninety-eight percent of these patients had experienced 2 or more hemorrhages associated with new neurological deficits. Seventeen patients (16.5%) had undergone attempted resection before radiosurgery. Ninety-three CCMs were located in deep brain structures and 10 were in subcortical lobar areas of functional brain importance. The median malformation volume was 1.31 ml, and the median tumor margin dose was 16 Gy. RESULTS: The follow-up ranged from 2 to 20 years. The annual hemorrhage rate--that is, a new neurological deficit associated with imaging evidence of a new hemorrhage--before SRS was 32.5%. After SRS 22 hemorrhages were observed within 2 years (10.8% annual hemorrhage rate) and 4 hemorrhages were observed after 2 years (1.06% annual hemorrhage rate). The risk of hemorrhage from a CCM was significantly reduced after radiosurgery (p < 0.0001). Overall, new neurological deficits due to adverse radiation effects following SRS developed in 14 patients (13.5%), with most occurring early in our experience. Modifications in technique (treatment volume within the T2-weighted MR imaging-defined margin, use of MR imaging, and dose reduction for CCM in critical brainstem locations) further reduced risks after SRS. CONCLUSIONS: Data in this study provide further evidence that SRS is a relatively safe procedure that reduces the rebleeding rate for CCMs located in high-surgical-risk areas of the brain.

OBJECT: Because of their critical location adjacent to brain, cranial nerve, and vascular structures, petroclival meningiomas remain a clinical challenge. The authors evaluated outcomes in 168 patients with petroclival meningiomas who underwent Gamma Knife surgery (GKS) during a 21-year interval. METHODS: Gamma Knife surgery was used as either primary or adjuvant treatment of 168 petroclival meningiomas involving the region between the petrous apex and the upper two-thirds of the clivus. The most common presenting symptoms were trigeminal nerve dysfunction, balance problems, diplopia, and hearing loss. The median tumor volume was 6.1 cm3 (range 0.3-32.5 cm3), and the median radiation dose to the tumor margin was 13 Gy (range 9-18 Gy). RESULTS: During a median follow-up of 72 months, neurological status improved in 44 patients (26%), remained stable in 98 (58%), and worsened in 26 (15%). Tumor volume decreased in 78 patients (46%), remained stable in 74 (44%), and increased in 16 (10%), all of whom were subjected to additional management strategies. Overall 5- and 10-year progression-free survival rates were 91 and 86%, respectively. Patients followed up for at least 10 years (31 patients) had tumor and symptom control rates of 97 and 94%, respectively. Eight patients had repeat radiosurgery, 4 underwent delayed resection, and 4 had fractionated radiation therapy. Cerebrospinal fluid diversion was performed in 7 patients (4%). Significant risk factors for tumor progression were a tumor volume > or = 8 cm3 (p = 0.001) and male sex (p = 0.02). CONCLUSIONS: In this 21-year experience, GKS for petroclival meningiomas obviated initial or further resection in 98% of patients and was associated with a low risk of adverse radiation effects. The authors believe that radiosurgery should be considered as an initial option for patients with smaller-volume, symptomatic petroclival meningiomas.

OBJECT: Trigeminal neuralgia pain causes severe disability. Stereotactic radiosurgery is the least invasive surgical option for patients with trigeminal neuralgia. Since different medical and surgical options have different rates of pain relief and morbidity, it is important to evaluate longer-term outcomes. METHODS: The authors retrospectively reviewed outcomes in 503 medically refractory patients with trigeminal neuralgia who underwent Gamma Knife surgery (GKS). The median patient age was 72 years (range 26-95 years). Prior surgery had failed in 205 patients (43%). The GKS typically was performed using MR imaging guidance, a single 4-mm isocenter, and a maximum dose of 80 Gy. RESULTS: Patients were evaluated for up to 16 years after GKS; 107 patients had > 5 years of follow-up. Eighty-nine percent of patients achieved initial pain relief that was adequate or better, with or without medications (Barrow Neurological Institute [BNI] Scores I-IIIb). Significant pain relief (BNI Scores I-IIIa) was achieved in 73% at 1 year, 65% at 2 years, and 41% at 5 years. Including Score IIIb (pain adequately controlled with medication), a BNI score of I-IIIb was found in 80% at 1 year, 71% at 3 years, 46% at 5 years, and 30% at 10 years. A faster initial pain response including adequate and some pain relief was seen in patients with trigeminal neuralgia without additional symptoms, patients without prior surgery, and patients with a pain duration of < or = 3 years. One hundred ninety-three (43%) of 450 patients who achieved initial pain relief reported some recurrent pain 3-144 months after initial relief (median 50 months). Factors associated with earlier pain recurrence that failed to maintain adequate or some pain relief were trigeminal neuralgia with additional symptoms and > or = 3 prior failed surgical procedures. Fifty-three patients (10.5%) developed new or increased subjective facial paresthesias or numbness and 1 developed deafferentation pain; these symptoms resolved in 17 patients. Those who developed sensory loss had better long-term pain control (78% at 5 years). CONCLUSIONS: Gamma Knife surgery proved to be safe and effective in the treatment of medically refractory trigeminal neuralgia and is of value for initial or recurrent pain management. Despite the goal of minimizing sensory loss with this procedure, some sensory loss may improve long-term outcomes. Pain relapse is amenable to additional GKS or another procedure.