Background:In the midbrain of patients with Parkinson disease (PD), there is a selective loss of

To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify non-invasive measures of basal ganglia function that are sensitive to disease severity. This study examines the relation between blood oxygenation level dependent (BOLD) activation in every nucleus of the basal ganglia and symptom-specific disease severity in early stage, de novo PD. BOLD activation measured at 3 Tesla was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the basal ganglia nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified Parkinson's Disease Rating Scale (UPDRS) and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the basal ganglia and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the basal ganglia relates most consistently to bradykinesia. The findings demonstrate that functional magnetic resonance imaging has strong potential to serve as a non-invasive marker for the state of basal ganglia function in de novo PD.

favorably to such hypofractionation. In this study, we evaluate outcomes after SBRT in patients with metastatic melanoma. Materials/Methods: A retrospective review of all cases of metastatic melanoma treated with SBRT at the study institution was conducted. Tumors were excluded if they were located in the brain, or had less than 3 months follow-up. 20 consecutively treated patients (34 tumors) were identified. SBRT was delivered with fiducial and vertebral anatomy-based targeting to metastatic lesions in the chest (n Z 16), spine (n Z 9), pelvis/ abdomen (n Z 6), H&N (n Z 2), and liver (n Z 1). Six cases of SBRT (5 spine, 1 chest) were in previously irradiated sites, and seven tumors were oligometastases. Radiation dose ranged from 8 Gy x 1 fraction to 9 Gy x 5 fractions; the most common regimen was 8 Gy x 3 (n Z 10). Median treated volume was 46.4 cm 3 (range, 7.8-455.7 cm 3 ). Results: Median follow-up was 20.7 months (range, 3-60.4 months) and median age at time of radiation was 49 (range, 28-88 years). At time of last follow-up, 8 patients were still alive and 12 had died, with median survival of 22.3 months from time of SBRT. Overall, 80% of patients achieved local control; tumor progression was noted in 8 sites at a median time to failure of 19.7 months (range, 2.1 e 34.3 months). All cases of tumor progression occurred in the lung, in patients who developed uncontrolled systemic disease. Site (log-rank p Z 0.008) and size of treated volume (log-rank p Z 0.045) were significant for local control on univariate analysis. No cases of radiation-induced toxicity occurred. Conclusions: SBRT is an acceptable treatment choice for metastatic melanoma, providing durable local tumor control with limited morbidity. Tumors that are larger in size, or located in the lung, had decreased likelihood of long-term control.