Abstract :
Although the neurochemical lesion in Parkinsonʹs Disease is mainly localized to the nigrostriatal dopamine system, the effects are widespread and affect non-dopaminoceptive neurons in other brain regions. Two innovative approaches have emerged to surgically treat this condition. The first method involves replacing degenerating dopaminergic neurons with embryonic nigral grafts that can express dopamine in vivo. Fetal dopaminergic cells are implanted directly into the putamen - the target of most nigral dopaminergic projections. Tissue engraftment can be assessed by the striatal uptake of 18F-fluorodopa with PET as an index of local neuronal decarboxylase activity. We have demonstrated successful tissue engraftment by PET and quantitative clinical performance measures as early as one year post-transplant. Many advanced patients develop a gradual decline in the efficacy of dopaminergic therapies. Because many of the motor manifestations relate to enhanced inhibition of the motor thalamus by an overactive globus pallidus, pallidal ablation may be helpful. We have found evidence for this in comparative studies of regional brain metabolism before and subsequent to ventral pallidotomy. Our findings indicated that motor improvement is mediated by changes in the expression of pathological brain networks linking the pallidum, thalamus and motor cortices. This method may allow for better tolerance of dopaminergic medications, as well as improved motor performance in the untreated state. These surgical approaches to the treatment of Parkinsonʹs Disease represent an innovative first step. Future approaches involving the implantation of genetically engineered cells, or the stereotaxic placement of pallidal and/or thalamic stimulators hold great promise.
