Parkinson's Disease: deep brain stimulation and FDOPA-PET

Parkinson’s Disease (PD) is characterised by the progressive death of selected heterogeneous populations of neurons, including dopaminergic neurons in the mesencephalon. The etiology of PD is unknown but likely results from complex environmental and genetic interactions. Clinically, the typical PD motor features (bradykinesia, rigidity, rest tremor and eventually postural instability) often are accompanied by cognitive symptomatology. Current treatment in PD is symptomatic and basically focussed on motor symptom control. However, since PD progresses over time nowadays a major therapeutic aim is the halting of the underlying and ongoing disease process. Chronic bilateral Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) has shown to improve motor features sufficiently in a selected population of PD patients. Since glutamatemediated excitotoxicity of the hyperactive STN is suggested to contribute to nigrostriatal degeneration in PD, the clinical introduction of STN-DBS also provided an opportunity to functionally inhibit STN activity and therefore decrease disease progression. Positron Emission Tomography (PET), using the tracer FDOPA, has provided an objective means of assessing the functional integrity of the presynaptic nigrostriatal dopaminergic projections in vivo. Besides discriminating PD from normal populations, FDOPA-PET has shown to be an objective monitor of disease progression in PD. The primary aim of this thesis was to prospectively determine disease progression in a population of PD patients after STN-DBS by means of repetitive FDOPA-PET. In addition, the evaluation of the clinical efficacy of STN-DBS on motor features in advanced PD was studied. In another study we assessed the nature of the relationship between striatal dopamine activity and cognitive impairments in PD using FDOPAPET and neuropsychological data. Finally, we sought to determine the predictive value of the patients’ presurgical nigrostriatal status on motor efficacy of STN-DBS in PD using FDOPA-PET.