Marie Meyer1,2, Frédéric Lamare1,2, Julien Asselineau3, Alexandra Foubert-Samier4,5,6,7, Joachim Mazère1,2, Paolo Zanotti-Fregonara1,2, Gaia Rizzo8, Anna Delamarre5,7, Umberto Spampinato4, Olivier Rascol9,10, Anne Pavy-Le Traon9,11, François Tison4,5,7, Philippe Fernandez1,2, Igor Sibon4, Wassilios G Meissner4,5,7,12. 1. Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France. 2. Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France. 3. Public Health Department, Clinical Epidemiology Unit, Bordeaux University Hospital, Bordeaux, France. 4. Service de Neurologie, CHU Bordeaux, Bordeaux, France. 5. French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France. 6. Inserm, UMR1219, Bordeaux Population Health Research Center, Bordeaux University, ISPED, Bordeaux, France. 7. Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France. 8. Invicro and Division of Brain Sciences, Imperial College London, London, UK. 9. French Reference Centre for MSA, University Hospital Toulouse, Toulouse, France. 10. Clinical Investigation Center CIC 1436 and Departments of Neurosciences and Clinical Pharmacology, Inserm, Toulouse University and CHU Toulouse, Toulouse, France. 11. Institut des Maladies Métaboliques et Cardiovasculaires, Inserm U 1048, Toulouse University, Toulouse, France. 12. Department of Medicine, University of Otago, Christchurch, and New Zealand Brain Research Institute, Christchurch, New Zealand.
Abstract
BACKGROUND: Loss of medullary serotonin (5-hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5-hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5-hydroxytryptamine1A receptor binding between MSA and healthy controls. Secondary objectives were to compare 5-hydroxytryptamine1A receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA. METHODS: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18). RESULTS: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA. CONCLUSION: Our results demonstrate 5-hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy.
BACKGROUND: Loss of medullary serotonin (5-hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5-hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5-hydroxytryptamine1A receptor binding between MSA and healthy controls. Secondary objectives were to compare 5-hydroxytryptamine1A receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA. METHODS: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18). RESULTS: 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA. CONCLUSION: Our results demonstrate 5-hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy.