Faculty Bibliography

OBJECT: The surgical management of disabling tremor has gained renewed vigor with the availability of deep brain stimulation. However, in the face of an aging population of patients with increasing surgical comorbidities, noninvasive approaches for tremor management are needed. The authors' purpose was to study the technique and results of stereotactic radiosurgery performed in the era of MRI targeting. METHODS: The authors evaluated outcomes in 86 patients (mean age 71 years; number of procedures 88) who underwent a unilateral Gamma Knife thalamotomy (GKT) for tremor during a 15-year period that spanned the era of MRI-based target selection (1996-2011). Symptoms were related to essential tremor in 48 patients (19 age >/= 80 years and 3 age >/= 90 years), Parkinson disease in 27 patients (11 age >/= 80 years [1 patient underwent bilateral procedures]), and multiple sclerosis in 11 patients (1 patient underwent bilateral procedures). A single 4-mm isocenter was used to deliver a maximum dose of 140 Gy to the posterior-inferior region of the nucleus ventralis intermedius. The Fahn-Tolosa-Marin clinical tremor rating scale was used to grade tremor, handwriting, and ability to drink. The median follow-up was 23 months. RESULTS: The mean tremor score was 3.28 +/- 0.79 before and 1.81 +/- 1.15 after (p < 0.0001) GKT; the mean handwriting score was 2.78 +/- 0.82 and 1.62 +/- 1.04, respectively (p < 0.0001); and the mean drinking score was 3.14 +/- 0.78 and 1.80 +/- 1.15, respectively (p < 0.0001). After GKT, 57 patients (66%) showed improvement in all 3 scores, 11 patients (13%) in 2 scores, and 2 patients (2%) in just 1 score. In 16 patients (19%) there was a failure to improve in any score. Two patients developed a temporary contralateral hemiparesis, 1 patient noted dysphagia, and 1 sustained facial sensory loss. CONCLUSIONS: Gamma Knife thalamotomy in the MRI era was a safe and effective noninvasive surgical strategy for medically refractory tremor in the elderly or those with contraindications to deep brain stimulation or stereotactic radiofrequency (thermal) thalamotomy.

We evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm(3) (range 0.3-11.6). The marginal tumor dose (median = 15 Gy, range 12-25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12-185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined as a decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six (27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy.

BACKGROUND: As systemic therapies improve and patients live longer, concerns mount about the toxicity of whole-brain radiation therapy (WBRT) for treatment of brain metastases. Development of delayed white matter abnormalities indicative of leukoencephalopathy have been correlated with cognitive dysfunction. This study assesses the risk of imaging-defined leukoencephalopathy in patients whose management included WBRT in addition to stereotactic radiosurgery (SRS). This risk is compared to patients who only underwent SRS. METHODS: We retrospectively compared 37 patients with non-small cell lung cancer who underwent WBRT plus SRS to 31 patients who underwent only SRS. All patients survived at least 1 year after treatment. We graded the development of delayed white matter changes on magnetic resonance imaging using a scale to evaluate T(2) /FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity; grade 2 = limited periventricular hyperintensity; and grade 3 = diffuse white matter hyperintensity. RESULTS: Patients treated with WBRT and SRS had a significantly greater incidence of delayed white matter leukoencephalopathy compared to patients who underwent SRS alone (P < .001). On final imaging, 36 of 37 patients (97.3%) treated by WBRT developed leukoencephalopathy (25% with grade 2; 70.8% with grade 3). Only 1 patient treated with SRS alone developed leukoencephalopathy. CONCLUSIONS: Risk of leukoencephalopathy in patients treated with SRS alone for brain metastases was significantly lower than that for patients treated with WBRT plus SRS. A prospective study is necessary to correlate these findings with neurocognition and quality of life. These data supplement existing reports regarding the differential effects of WBRT and SRS on normal brain structure and function. Cancer 2012. (c) 2012 American Cancer Society.

Object The first North American 201 cobalt-60 source Gamma Knife surgery (GKS) device was introduced at the University of Pittsburgh Medical Center in 1987. The introduction of this innovative and largely untested surgical procedure prompted the desire to study patient outcomes and evaluate the effectiveness of this technique. The parallel advances in computer software and database technology led to the development of a registry to track patient outcomes at this center. The purpose of this study was to describe the registry's evolution and to evaluate its usefulness. Methods A team was created to develop a software database and tracking system to organize and retain information on the usage of GKS. All patients undergoing GKS were systematically entered into this database by a clinician familiar with the technology and the clinical indications. Information included patient demographics and diagnosis as well as the anatomical site of the target and details of the procedure. Results There are currently 11,738 patients in the database, which began to be used in August 1987. The University of Pittsburgh Medical Center has pioneered the evaluation and publication of the GKS technique and outcomes. Data derived from this computer database have facilitated the publication of more than 400 peer-reviewed manuscripts, more than 200 book chapters, 8 books, and more than 300 published abstracts and scientific presentations. The use of GKS has become a well-established surgical technique that has been performed more than 700,000 times around the world. Conclusions The development of a patient registry to track and analyze the use of GKS has given investigators the ability to study patient procedures and outcomes. The future of clinical medical research will rely on the ability of clinical centers to store and to share information.

Treatment options for symptomatic dural arteriovenous fistulas (DAVFs) include surgery, embolization and stereotactic radiosurgery (SRS). We reviewed our DAVF experience at the University of Pittsburgh and assessed the role of SRS. We evaluated 40 consecutive patients who underwent Gamma Knife SRS for 44 DAVFs. Twenty-eight patients had upfront SRS before or after embolization performed at our institution, and 12 patients underwent delayed SRS for recurrent or residual DAVFs after initial embolization. The median SRS target volume was 2.0 cm(3), and the median marginal dose was 21.0 Gy. At a median follow-up of 45 months (range, 23-116 months), a total of 28 patients with 32 DAVFs had obliteration. The obliteration rate was 83% for patients who had upfront SRS and embolization. The obliteration rate was lower (67%) for patients managed with SRS alone. The obliteration rate was 71% for patients who had delayed SRS for recurrent or residual DAVFs following prior embolization. In our experience cavernous/carotid fistulas were associated with higher rates of obliteration and symptomatic improvement compared to transverse/sigmoid sinus region fistulas. Our experience suggests that successful DAVF obliteration is possible in most patients with upfront SRS in conjunction with embolization. SRS alone is an effective treatment for selected patients with a small-volume, low-risk DAVF.

Over the last two decades, stereotactic radiosurgery (SRS) has become a mainstay in the management of arteriovenous malformations (AVMs) of the brain. An extensive collective experience has demonstrated that SRS is a minimally invasive technique that can produce excellent AVM obliteration rates with only a modest risk of permanent adverse radiation effects (AREs). Controversy remains regarding the optimal treatment approach for AVMs, with much of the debate centered upon the risk:benefit ratios of microsurgical resection versus SRS. Proponents of surgery suggest that for appropriate Spetzler-Martin grade AVMs microsurgery harbors minimal morbidity and immediate cure. In contrast, supporters of SRS argue that many AVMs cannot be treated by microsurgery with limited morbidity, and that despite the possibility of hemorrhage during the latency to obliteration, the risk profile of SRS is more favorable. Unfortunately, a randomized clinic trial comparing microsurgery and SRS is not likely, so clinicians and patients must use available data to make their own decisions. Much effort has been expended to identify factors associated with AREs, defining their impact and predicting which patients are likely to have complete AVM obliteration in the absence of new neurological deficits. Refinement in an AVM management algorithm on these bases should better educate clinicians and patients about risk profiles, improve patient selection for different treatment strategies, and increase the likelihood of good therapeutic outcomes. Herein, we give a definition to the term ARE and review the suspected mechanisms that lead to them.