Samuel A. Ellias

Transplantation of embryonic porcine mesencephalic tissue in patients with PD

Objective: To assess the safety and the effect on standardized clinical rating measures of transplanted embryonic porcine ventral mesencephalic (VM) tissue in advanced PD. Methods: Twelve patients with idiopathic PD underwent unilateral implantation of embryonic porcine VM tissue; six received cyclosporine immunosuppression and six received tissue treated with a monoclonal antibody directed against major histocompatibility complex class I. Patients were followed for 12 months and assessed by clinical examination, MRI, and 18F-levodopa PET. Porcine endogenous retrovirus testing was conducted by PCR-based method on peripheral blood mononuclear cells. Results: Cell implantation occurred without serious adverse events in all patients. Cultures were negative for bacterial and unknown viral contamination. No porcine endogenous retrovirus DNA sequences were found. MRI demonstrated cannula tracts within the putamen and caudate, with minimal or no edema and no mass effect at the transplant sites. In the medication-off state, total Unified Parkinson’s Disease Rating Scale scores improved 19% (p = 0.01). Three patients improved over 30%. There were two patients with improved gait. 18F-levodopa PET failed to show changes on the transplanted side. Conclusions: Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical PD rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue.

The dendritic varicosity: a mechanism for electrically isolating the dendrites of cat retinal amacrine cells?

Amacrine dendritic varicosities from cat retina were reconstructed using serial electron micrographs. Each varicosity contained a synaptic input and a synaptic output, suggesting that they may function as isolated local circuits. A passive steady state electrical model demonstrated that for a given conductance change the varicose dendrite maximizes the local membrane potential and minimizes th distance membrane potential change as compared to other possible dendritic shapes. We, therefore, suggest that the function of the varicosities on amacrine cell dendrites might be to electrically isolate these local input-output circuits.

Isolation of the brain-related factor of the error between intended and achieved position of deep brain stimulation electrodes implanted into the subthalamic nucleus for the treatment of Parkinson's disease.

OBJECTIVE Although a few studies have quantified errors in the implantation of deep brain stimulation electrodes into the subthalamic nucleus (STN), a significant trend in error direction has not been reported. We have previously found that an error in axial plane, which is of most concern because it cannot be compensated for during deep brain stimulation programming, had a posteromedial trend. We hypothesized that this trend results from a predominance of a directionally oriented error factor of brain origin. Accordingly, elimination of nonbrain (technical) error factors could augment this trend. Thus, implantation accuracy could be improved by anterolateral compensation during target planning. METHODS Surgical technique was revised to minimize technical error factors. During 22 implantations, targets were selected on axial magnetic resonance imaging scans up to 1.5 mm anterolateral from the STN center. Using fusion of postoperative computed tomographic and preoperative magnetic resonance imaging scans, implantation errors in the axial plane were obtained and compared with distances from the lead to the STN to evaluate the benefit of anterolateral compensation. RESULTS Twenty errors and the mean error had a posteromedial direction. The average distances from the lead to the target and to the STN were 1.7 mm (range, 0.8–3.1 mm) and 1.1 mm (range, 0.1–1.9 mm), respectively. The difference between the 2 distances was significant (paired t test, P < 0.0001). The lower parts of the lead were consistently bent in the posteromedial direction on postoperative scout computed tomographic scans, suggesting that a brain-related factor is responsible for the reported error. CONCLUSION Elimination of the technical factors of error during STN deep brain stimulation implantation can result in a consistent posteromedial error. Implantation accuracy may be improved by compensation for this error in advance.