[¹⁸F]FDOPA PET and clinical features in parkinsonism due to manganism

Abstract

Manganese exposure reportedly causes a clinically and pathophysiologically distinct syndrome from idiopathic Parkinson's disease (PD). We describe the clinical features and results of positron emission tomography with 6-[18F]fluorodopa ([18F]FDOPA PET) of a patient with parkinsonism occurring in the setting of elevated blood manganese. The patient developed parkinsonism associated with elevated serum manganese from hepatic dysfunction. [18F]FDOPA PET demonstrated relatively symmetric and severely reduced [18F]FDOPA levels in the posterior putamen compared to controls. The globus pallidum interna had increased signal on T1-weighted magnetic resonance imaging (MRI) images. We conclude that elevated manganese exposure may be associated with reduced striatal [18F]FDOPA uptake, and MRI may reveal selective abnormality within the internal segment of the pallidum. This case suggests that the clinical and pathophysiological features of manganese-associated parkinsonism may overlap with that of PD.

Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

“…Several studies have reported that L-DOPA treatment was effective in cases of manganese poisoning (Huang et al 1989;Mena et al 1970;Rosenstock et al 1971), while other (double-blind) studies have reported that L-DOPA therapy 22 was ineffective in the treatment of motor dysfunction associated with high manganese exposure (Koller et al 2004;Lu et al 1994). These observations are consistent with the proposition that dopamine depletion emerges as the ultimate effect on the dopaminergic system, though this effect may be preceded by changes in other parameters, such as dopamine receptor affinity and density (Shinotoh et al 1997), dopamine reuptake ability (Kim et al 2005;Racette et al 2005b), dopamine production or dopamine vesicular storage.…”

“…This raises the intriguing possibility that manganese exposure may both induce atypical Parkinsonism (based on pallidal effects) and contribute to more typical Parkinsonism (based on dopaminergic effects). While a distinction has been made between the motor effects induced by manganese exposure and those observed in Parkinson's disease , a few recent studies propose a higher incidence of Parkinson's disease in workers occupationally exposed to manganese (Gorell et al 1999;Racette et al 2005b). Manganese exposure could be a risk factor of Parkinson's disease if manganese were to accelerate depletion of striatal dopamine after sustained occupational exposure, and precipitate the appearance of Parkinson's disease like-symptoms.…”

Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures

“…Recent studies suggest that the prevalence of Parkinsonism is higher among welders vs. age-standardized individuals in the general population (Racette et al, 2001;2005a). Finally, positron emission tomography (PET) in a welder with Parkinsonism confirms that the clinical features of Mn-induced Parkinsonism overlap with those of PD, characterized by prolonged L-dopa responsiveness and reduced [ 18 F]fluorodopa uptake (Racette et al, 2005b).…”

Neuroimaging in Manganese-Induced Parkinsonism

“…Four of five patients showed atypical parkinsonism, with normal DAT density, which could be clearly differentiated from PD, whereas one patient showed levodopa-responsive parkinsonism with reduced DAT density (classical PD). These findings are remarkably different from those of Racette et al (2005). PET/SPECT findings in patients with manganism caused by liver failure should be further studied, with respect to both clinical and pathological features.…”

“…However, Guilarte et al (2008) reported that, in the non-human primate brain, chronic Mn exposure inhibited dopaminergic transmission, leading to motor deficits, in the absence of changes to presynaptic dopaminergic nerve terminals. Racette et al (2005) found relatively symmetrical and severely reduced fluorodopa uptake on PET in the posterior putamen of a patient with manganism secondary to liver failure, together with T1 hyperintensities in the basal ganglia on MRI. This is the only reported case of secondary manganism accompanied by abnormal fluorodopa PET findings.…”