Abstract
Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented. Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism. Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels. Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
Highlights
Parkinson’s disease (PD) is a neurological condition with loss of dopamine (DA) producing neurons in the substantia nigra (SN) of the basal ganglia (BG)
In a previous study our group investigated the effect of Deep brain stimulation (DBS) of the subthalamic nucleus (STN) on different neurotransmitters in the BG in PD patients to learn more about the mechanisms of DBS [28] using perioperative stereotactic microdialysis, which is a method for measuring concentrations of neurotransmitters in the human brain [29]-[35]
Left STN DBS was performed during fraction 9 - 11 and the levodopa levels decreased during these fractions
Summary
Parkinson’s disease (PD) is a neurological condition with loss of dopamine (DA) producing neurons in the substantia nigra (SN) of the basal ganglia (BG). Unlike DA, crosses the blood-brain-barrier (BBB) and is given together with a dopa decarboxylase inhibitor (DDI), to avoid high peripheral levodopa metabolism and elevated DA concentrations causing side effects such as nausea, orthostatic hypotension and vomiting. The mechanisms of LID are not completely understood but in rat models it has been shown that intermittent levodopa treatment combined with degeneration of tyrosin hydroxylase containing neurons induces dyskinesia while continuously given levodopa (continuous dopaminergic stimulation = CDS) reduces LID [12] [16] [17] [18]. Deep brain stimulation (DBS) has been shown effective in reducing motor symptoms and in decreasing the daily doses of dopaminergic drugs in PD patients [19]-[25] with maintained effect several years after the surgical intervention [25] [26]. In a previous study our group investigated the effect of DBS of the subthalamic nucleus (STN) on different neurotransmitters in the BG in PD patients to learn more about the mechanisms of DBS [28] using perioperative stereotactic microdialysis, which is a method for measuring concentrations of neurotransmitters in the human brain [29]-[35]
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