Faculty Bibliography

BACKGROUND: Idiopathic Parkinson's disease can present with symptoms similar to those of multiple system atrophy or progressive supranuclear palsy. We aimed to assess whether metabolic brain imaging combined with spatial covariance analysis could accurately discriminate patients with parkinsonism who had different underlying disorders. METHODS: Between January, 1998, and December, 2006, patients from the New York area who had parkinsonian features but uncertain clinical diagnosis had fluorine-18-labelled-fluorodeoxyglucose-PET at The Feinstein Institute for Medical Research. We developed an automated image-based classification procedure to differentiate individual patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. For each patient, the likelihood of having each of the three diseases was calculated by use of multiple disease-related patterns with logistic regression and leave-one-out cross-validation. Each patient was classified according to criteria defined by receiver-operating-characteristic analysis. After imaging, patients were assessed by blinded movement disorders specialists for a mean of 2.6 years before a final clinical diagnosis was made. The accuracy of the initial image-based classification was assessed by comparison with the final clinical diagnosis. FINDINGS: 167 patients were assessed. Image-based classification for idiopathic Parkinson's disease had 84% sensitivity, 97% specificity, 98% positive predictive value (PPV), and 82% negative predictive value (NPV). Imaging classifications were also accurate for multiple system atrophy (85% sensitivity, 96% specificity, 97% PPV, and 83% NPV) and progressive supranuclear palsy (88% sensitivity, 94% specificity, 91% PPV, and 92% NPV). INTERPRETATION: Automated image-based classification has high specificity in distinguishing between parkinsonian disorders and could help in selecting treatment for early-stage patients and identifying participants for clinical trials. FUNDING: National Institutes of Health and General Clinical Research Center at The Feinstein Institute for Medical Research

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson's disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity

The authors demonstrate that high-frequency electrical stimulation dorsal to the subthalamic nucleus (STN) can directly suppress levodopa-induced dyskinesias. This 63-year-old woman with idiopathic Parkinson disease underwent surgery for placement of bilateral subthalamic deep brain stimulation (DBS) electrodes to control progressive rigidity, motor fluctuations, and levodopa-induced dyskinesias. The model 3389 DBS leads were implanted with microelectrode guidance. Magnetic resonance imaging confirmed proper placement of the leads. Postoperatively the patient exhibited improvement in all of her parkinsonian symptoms; however, her right leg dyskinesias had not improved. Based on their previous experiences treating levodopa-induced dyskinesias with subthalamic stimulation through the more dorsally located contacts of the model 3387 lead, the authors withdrew the implanted 3389 lead 3 mm. Following relocation of the lead they were able to suppress the right leg dyskinesias by using the most dorsal contacts. The patient's dopaminergic medication intake increased slightly. These findings indicate that electrical stimulation dorsal to the STN can directly suppress levodopa-induced dyskinesias independent of dopaminergic medication changes. The 3389 lead may provide inadequate coverage of the subthalamic region for some patients.