Abstract
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia). Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.
Highlights
Idiopathic Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons of the subtantia nigra pars compacta, and clinically diagnosed on the basis of a motor symptomatology: tremor, rigidity and/or bradykynesia.PD clinical diagnosis is prone to errors [1,2], as this array of motor symptoms is present in a wide range of other parkinsonian conditions such as progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy
When comparing the modulated white matter (WM) maps of the healthy control with the PD group, a single symmetrical cluster was found, in the caudal part of the pons, overlapping with the rostral medulla oblongata
The goal of the study was to characterize the volume reduction pattern in white matter associated with PD
Summary
Idiopathic Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons of the subtantia nigra pars compacta, and clinically diagnosed on the basis of a motor symptomatology: tremor, rigidity and/or bradykynesia.PD clinical diagnosis is prone to errors [1,2], as this array of motor symptoms is present in a wide range of other parkinsonian conditions such as progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy. Recent analysis methods based on structural MRI (T1-weighted contrast, diffusion tensor imaging [3]) have been able to exhibit significant differences between demented and non-demented PD patients [4,5], or between PD and PSP [6] or dementia with Lewy bodies patients [7]. While these studies brought some insight to the differential diagnosis of these various diseases, they have been unable so far to clearly distinguish PD patients from healthy controls [8,9]
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