Laurène Leclair-Visonneau1, Thomas Clairembault2, Christelle Volteau3, Guillaume Chapelet4, Séverine Le Dily5, Fabienne Vavasseur5, Emmanuel Coron6, Cécile Préterre7, Michel Neunlist8, Yann Péréon9, Pascal Derkinderen7. 1. Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; Inserm, CIC-04, CHU de Nantes, Bd Jacques Monod, F-44093, Nantes, France; CHU Nantes, Department of Clinical Neurophysiology, Bd Jacques Monod, F-44093, Nantes, France. Electronic address: laurene.leclair@chu-nantes.fr. 2. Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France. 3. CHU Nantes, Plateforme de Biométrie, département Promotion DRCI, 1 Place Alexis Ricordeau, F-44093, Nantes, France. 4. University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; CHU Nantes, Clinical Gerontology Department, Bd Jacques Monod, F-44093, Nantes, France. 5. Inserm, CIC-04, CHU de Nantes, Bd Jacques Monod, F-44093, Nantes, France. 6. Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; Inserm, CIC-04, CHU de Nantes, Bd Jacques Monod, F-44093, Nantes, France; CHU Nantes, Institut des Maladies de l'Appareil Digestif, 1 Place Alexis Ricordeau, F-44093, Nantes, France. 7. Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; Inserm, CIC-04, CHU de Nantes, Bd Jacques Monod, F-44093, Nantes, France; CHU Nantes, Department of Neurology, Nantes, Bd Jacques Monod, F-44093, Nantes, France. 8. Inserm, U1235, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; CHU Nantes, Institut des Maladies de l'Appareil Digestif, 1 Place Alexis Ricordeau, F-44093, Nantes, France. 9. University Nantes, Faculté de Médecine, 1 rue Gaston Veil, F-44035, Nantes, France; CHU Nantes, Department of Clinical Neurophysiology, Bd Jacques Monod, F-44093, Nantes, France.
Abstract
INTRODUCTION: Dysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonic alpha-synuclein histopathology is associated with dysautonomia in PD. METHODS: A total of 43 PD patients participated in this study. For each patient, two biopsies were taken in the sigmoid colon and analyzed by immunohistochemistry with antibodies against phosphorylated alpha-synuclein and PGP 9.5. All patients had a complete neuropsychological and neurological assessment along with a comprehensive evaluation of dysautonomia with questionnaires (SCOPA-Aut, NMS-Quest, Rome III constipation criteria and dry eye symptoms) and functional tests (pupillometry, Saxon and Schirmer's tests, heart rate variability, orthostatic blood pressure measure and sympathetic skin response). RESULTS: Colonic PASH was observed in 20/43 PD patients. No differences were observed in autonomic symptoms and testing between patients with and without PASH. CONCLUSIONS: Although frequent in PD, autonomic dysfunction is not related to colonic PASH. In addition to the existing literature, our findings further suggest that each dysautonomic symptom in PD might not be associated with a more severe or diffuse PASH not only in the central nervous system but also in the peripheral autonomic nervous systems.
INTRODUCTION:Dysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonicalpha-synuclein histopathology is associated with dysautonomia in PD. METHODS: A total of 43 PDpatients participated in this study. For each patient, two biopsies were taken in the sigmoid colon and analyzed by immunohistochemistry with antibodies against phosphorylated alpha-synuclein and PGP 9.5. All patients had a complete neuropsychological and neurological assessment along with a comprehensive evaluation of dysautonomia with questionnaires (SCOPA-Aut, NMS-Quest, Rome III constipation criteria and dry eye symptoms) and functional tests (pupillometry, Saxon and Schirmer's tests, heart rate variability, orthostatic blood pressure measure and sympathetic skin response). RESULTS:ColonicPASH was observed in 20/43 PDpatients. No differences were observed in autonomic symptoms and testing between patients with and without PASH. CONCLUSIONS: Although frequent in PD, autonomic dysfunction is not related to colonicPASH. In addition to the existing literature, our findings further suggest that each dysautonomic symptom in PD might not be associated with a more severe or diffuse PASH not only in the central nervous system but also in the peripheral autonomic nervous systems.
Authors: Iris van der Lijn; Gera A de Haan; Famke Huizinga; Fleur E van der Feen; A Wijnand F Rutgers; Catherina Stellingwerf; Teus van Laar; Joost Heutink Journal: J Parkinsons Dis Date: 2022 Impact factor: 5.520