Multimodal assessment of gastric motility in subjects at (pre)clinical stages of Parkinsonīs Disease - A pathohistological and functional in-vivo-testing of Braak's pathoanatomical model
Rapid Response Innovation Awards, 2008
The research from this grant has continued with the supplementary grant:
Rapid eye movement (REM) sleep behaviour disorder (RBD) is a sleep disorder that presents with dream-enactments (vigorous movements, speech) during REM sleep. Patients with RBD frequently develop neurodegenerative disorders, particularly Parkinson’s disease. RBD is therefore considered as a risk marker for subsequent development of PD. This notion is consistent with the pathoanatomical model of PD proposed by Braak, who describes the chronology of the occurrence of PD-typical changes (Lewy bodies) in the central nervous system: brainstem areas known to regulate REM sleep are affected by the PD-typical Lewy body (LB) pathology before the first motor impairments occur. Early LB pathology is also seen in brainstem areas that are closely interconnected with the nervous system of the stomach that is responsible for gastric secretion and movements of the stomach. Indeed, the corresponding functional impairment (i.e. delayed emptying of the stomach) is common in PD. Interestingly, LB pathology has also been described in this nervous system of the stomach of PD patients and it is now hypothesized whether the disease might be even ignited there. However, little is known whether delayed emptying of the stomach is already present in early-stage PD. In RBD, emptying of the stomach has not yet been investigated. It is also unknown whether LB pathology is already present in the nervous system of the stomach of RBD patients.
After a standardized test meal, RBD patients, PD patients and healthy volunteers will be assessed with a breath test that allows detection of delayed gastric emptying. In addition, blood samples collected during this test will be analyzed for hormones that are known to regulate gastric motility. In subjects willing to undergo a gastroscopy, gastric mucosa specimens will be collected and analyzed for the presence of PD-typical pathological alterations (Lewy bodies) in the nervous systems of the stomach.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
By investigating disease-related functional impairments (i.e. delayed emptying of the stomach) and the underlying pathological alterations on the cell level, this project will expand our understanding of the pathological changes that occur in the very early phase of PD.
We expect to learn more about the link between RBD and PD. This project has the potential to prove for the first time in vivo that RBD (a condition considered as a risk marker for subsequent development of PD) and PD share the same pathological alterations on the cell level (Lewy bodies).
Senior Physician at Saarland University, Department of Neurology
Location: Homburg/Saar, Germany
Hertie-Senior-Research Professor at Philips University of Marburg
Location: Barcelona, Spain