Several groups have suggested the possibility of using early DBS to slow the pathologic progress of PD. Theoretically, glutamatergic projections from the STN to the substantia nigra pars compacta (SNc) represent an excitotoxic circuit. Thus, early dopaminergic loss causes increased STN activity, which, in turn, increases excitation and injury in the SNc. This process could have a similar toxic effect on the STN's other targets, including the GPi, substantia nigra pars reticulate (SNr), and PPN (14). This has been supported in rodent models demonstrating that previous STN ablation has a protective effect on the SNc from mitochondrial toxins known to cause dopaminergic attrition (27). This concept remains controversial, as there is no clear evidence supporting neuroprotection in human DBS subjects. It is not clear that STN DBS reduces glutamate output. Indeed, there is some evidence to the contrary. One study has demonstrated continued dopaminergic loss in the striatum of patients treated with STN DBS. In these patients, fluorodopa uptake decreased by 9% to 12% a year in 30 patients. This reduction is similar to known progression rates in unoperated patients (28). A multicenter trial is currently underway to assess the utility of early DBS treatment.
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