Faculty Bibliography

In an attempt to refine the indications for posteroventral pallidotomy (PVP) the authors instituted strict selection criteria which are based on the experience gained from the first 60 pallidotomy patients treated at their institution. In addition to clinical evaluation, all pallidotomy candidates undergo neuropsychological testing and 18F-fluoro-deoxyglucose utilization positron emission tomography (FDG/PET). The data from which these criteria were developed are presented as are early clinical results. The authors demonstrate that these criteria enhance the efficacy of the procedure by assuring therapeutic response and reducing the incidence of post-operative dementia. Their indications and contraindications for pallidotomy are discussed

A variety of clinical and experimental findings suggest that parkinsonian resting tremor results from the involuntary activation of a central mechanism normally used for the production of rapid voluntary alternating movements. However, such central motor loop oscillations have never been directly demonstrated in parkinsonian patients. Using magnetoencephalography, we recorded synchronized and tremor-related neuromagnetic activity over wide areas of the frontal and parietal cortex. The spatial and temporal organization of this activity was studied in seven patients suffering from early-stage idiopathic Parkinson's disease (PD). Single equivalent current dipole (ECD) analysis and fully three-dimensional distributed source solutions (magnetic field tomography, MFT) were used in this analysis. ECD and MFT solutions were superimposed on high-resolution MRI. The findings indicate that 3 to 6 Hz tremor in PD is accompanied by rhythmic subsequent electrical activation at the diencephalic level and in lateral premotor, somatomotor, and somatosensory cortex. Tremor-evoked magnetic activity can be attributed to source generators that were previously described for voluntary movements. The interference of such slow central motor loop oscillations with voluntary motor activity may therefore constitute a pathophysiologic link between tremor and bradykinesia in PD

Recently, there has been a surge in the research regarding the pharmacologic and surgical treatment of Parkinson's disease. This article reviews the latest modes of medical and surgical therapy for Parkinson's disease. The latest drug therapy has consisted of levodopa, a combination of levodopa and carbidopa (Sinemet/Sinemet CR), and monoamine oxidase type B (MAO-B) inhibitors (selegiline hydrochloride). The surgical treatment modalities have been stereotaxic implantations of dopamine-producing tissues (such as adrenal medulla and fetal mesencephalon) into the caudate nucleus and ventral pallidotomy of patients with Parkinson's disease. The most recent work has been in the field of gene therapy. The implantation of cells genetically modified to express trophic factors and tyrosine hydroxylase for the synthesis of L-dopa from tyrosine has been proposed as a possible route for the treatment of Parkinson's disease. Although the etiology of the disease is still unknown, two recent theories are discussed

Stereotaxic ventral pallidotomy has been employed in the symptomatic treatment of patients with advanced Parkinson's disease (PD). To understand the pathophysiology of clinical outcome following this procedure, we studied 10 PD patients (5 men and 5 women; mean age 60.0 +/- 6.1 years; mean Hoehn and Yahr stage 3.8 +/- 1.0) with quantitative 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). All patients were scanned preoperatively; 8 of 10 patients were rescanned 6 to 8 months following surgery. Clinical performance was assessed off medications before and after surgery using standardized timed motor tasks. We found that preoperative lentiform metabolism correlated significantly with improvement in contralateral motor tasks at 1 week, 3 months, and 6 months following unilateral pallidotomy (p<0.03). Postoperatively, significant metabolic increases were noted in the primary motor cortex, lateral premotor cortex, and dorsolateral prefrontal cortex (p<0.01) of the hemisphere that underwent surgery. Improvement in contralateral limb motor performance correlated significantly with surgical declines in thalamic metabolism (p<0.01) and increases in lateral frontal metabolism (p<0.05). Principal components analysis disclosed a significant covariance pattern characterized by postoperative declines in ipsilateral lentiform and thalamic metabolism associated with bilateral increase in supplementary motor control metabolism. Subject scores for this pattern correlated significantly with improvements in both contralateral and ipsilateral limb performance (p<0.005). These results suggest that pallidotomy reduced the preoperative overaction of the inhibitory pallidothalamic projection. Clinical improvement may be associated with modulations in regional brain metabolism occurring remote from the lesion site