Journal
PARKINSONISM & RELATED DISORDERS
Volume 91, Issue -, Pages 48-54Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2021.08.019
Keywords
Monoamine neurotransmitters; Myoclonus-dystonia; Dopa-responsive dystonia; Cervical dystonia; Non-motor symptoms
Categories
Funding
- Dystonia Medical Research Foundation (DMRF)
- Dystonie Wetenschapsfonds
- University of Groningen, University Medical Center Groningen
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This study revealed alterations in dopaminergic and serotonergic metabolism in patients with dystonia, with subtype-specific changes. Low levodopa concentrations, but not serotonin metabolites, were associated with both motor and non-motor symptoms.
Introduction: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the patho-physiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 mu mol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (r(s) = -0.3, p < 0.01), depression (r(s) = -0.3, p < 0.01) and fatigue (r(s) = -0.2, p = 0.04). Conclusion: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic me-tabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.
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