Central dopamine deficiency in pure autonomic failure

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Pure autonomic failure (PAF) and Parkinson's disease (PD) share clinical and laboratory findings.
• PAF is not typically associated with parkinsonism, a key feature of PD.
• The underlying reasons for the absence of motor symptoms in PAF compared to PD are not fully understood.

Purpose of the Study:

• To test the hypothesis that preserved nigrostriatal dopaminergic innervation in PAF accounts for the lack of motor dysfunction.
• To compare central and peripheral catecholamine systems in patients with PAF and PD.

Main Methods:

• Positron emission tomographic (PET) scanning using 6-[18F]fluorodopa was performed on patients with PAF (N=5), PD (N=21), and controls (N=14).
• Cerebrospinal fluid (CSF) catecholamine levels were measured.
• Postmortem tissue analysis of striatum, substantia nigra, and sympathetic ganglia was conducted in one patient with PAF and one with PD.

Main Results:

• Both PAF and PD groups exhibited similarly reduced 6-[18F]fluorodopa uptake in the substantia nigra (SN) relative to the occipital cortex (OCC), indicating severe central dopaminergic denervation.
• CSF levels of dihydroxyphenylacetic acid and DOPA were low in both groups.
• While both had low SN dopamine and tyrosine hydroxylase activity, PD showed significantly greater loss of dopamine in the putamen (PUT) compared to PAF.
• PAF patients had markedly lower myocardial norepinephrine concentrations than PD patients.

Conclusions:

• PAF and PD present with comparable severe nigral and central dopaminergic denervation.
• The greater loss of striatal dopaminergic terminals in PD explains its characteristic parkinsonism.
• The more pronounced loss of sympathetic noradrenergic terminals in PAF accounts for its autonomic dysfunction.
• Parkinsonism in PD is linked to striatal dopamine deficiency, not solely the loss of nigral dopaminergic neurons.