Faculty Bibliography

Cellular therapy has been evaluated in small animals, subhuman primates, and now humans for the potential repair of brain injury due to stroke. Experimental striate stroke models have proven useful for the purpose of evaluating different treatment paradigms. Early clinical trials involving neuronal transplantation in patients suffering motor-related stroke in the basal ganglia region have begun. This research will be described in this report.

Deep brain stimulation (DBS) has become a common therapeutic approach to patients with movement disorders. We evaluated results from two centers in a large metropolitan area where DBS systems are implanted into the thalamus for patients with tremor. Although all implanted systems led to an improvement in tremor, morbidity related to the hardware system occurred. A total of 23 hardware problems were noted in 66 patients undergoing implantation of 66 DBS systems (27% of patients). The most common problem included breakage of the electrode lead in its extracranial location, system infection, battery or connector problems, lead migration, and hemorrhage. Management was tailored to the specific hardware-related problem. Modifications in both surgical technique and hardware design should reduce the incidence of complications. Surgeons who place DBS systems should be aware of the spectrum of problems that can be associated with the device and its placement.

OBJECTIVE: To examine the role of stereotactic radiosurgery in the management of patients with progressive, well-circumscribed grade II fibrillary astrocytomas. METHODS: During a 13-year interval, 12 patients (median age: 25 years) required multimodality management for recurrent or unresectable World Health Organization (WHO) grade II fibrillary astrocytomas. Tumors involved the brainstem (n = 4), thalamus (n = 1), cerebellum (n = 1), frontal lobe (n = 4), temporal lobe (n = 1), and parietal lobe (n = 1). Diagnosis was confirmed by stereotactic biopsy (n = 5), partial resection (n = 5), and near total resection (n = 2). Multimodality management of patients prior to radiosurgery included fractionated radiation therapy (n = 4), stereotactic cyst drainage (n = 1), and ventriculoperitoneal shunt placement (n = 2). Tumor volumes varied from 1.2 to 45.1 cm(3). The median radiosurgical dose to the tumor margin was 16 Gy. RESULTS: After radiosurgery, serial imaging showed complete tumor resolution in 1 patient, reduced tumor volume in 4, stable tumor volume in 3, and delayed tumor progression in 4 (3 patients with increase in cyst size only). Therapy after radiosurgery included additional cytoreductive surgery (n = 1) for recurrence of a higher grade tumor, stereotactic cyst aspiration (n = 1), and stereotactic intracavitary irradiation (n = 1). All patients were alive at a median follow-up of 52 months after radiosurgery and 103 months after diagnosis. In 8 patients, follow-up lasted more than 60 months. CONCLUSION: Stereotactic radiosurgery is a potential alternative or adjunctive strategy in the management of selected patients with WHO grade II fibrillary astrocytomas.

OBJECT: Lung carcinoma is the leading cause of death from cancer. More than 25% of those patients with lung cancer develop a brain metastasis at some time during the course of their disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival for patients with lung carcinoma metastasis is approximately 3 to 6 months. The authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non-small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors affecting long-term patient survival. METHODS: A retrospective review of 273 patients who had undergone GKS to treat a total of 627 NSCLC metastases was performed. Clinical and neuroimaging data encompassing a 14-year treatment interval were collected. Univariate and multivariate analyses were performed to determine significant prognostic factors influencing patient survival. The overall median patient survival time was 15 months (range 1-116 months) from the diagnosis of brain metastases. The median survival was 10 months from GKS treatment in those patients with adenocarcinoma and 7 months for those with other histological tumor types. In patients with no active extracranial disease at the time of GKS, the median survival time was 16 months. In multivariate analyses, factors significantly affecting survival included: 1) female sex (p = 0.014); 2) preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and 5) time from lung cancer diagnosis to the development of brain metastasis (p = 0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate with extended patient survival time. Postradiosurgical imaging of brain metastases revealed that 60% decreased, 24% remained stable, and 16% eventually increased in size. Factors affecting local tumor control included tumor volume (p = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later underwent craniotomy and tumor resection for tumor refractory to GKS or a new symptomatic metastasis. CONCLUSIONS: Gamma knife surgery for NSCLC metastases affords effective local tumor control in approximately 84% of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including GKS can afford patients an extended survival time.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.