Regional Brain Stem Atrophy in Idiopathic Parkinson's Disease Detected by Anatomical MRI

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

Effect size at the peak of significance.

<p>Boxplot of the peak of significance value (arbitrary unit) for each participant in both groups, as obtained by SPM5 ‘fitted response’ plot function. Peak value was adjusted, meaning that the effect of age, gender and global WM volume were factored out, and only the effect of condition (Parkinson or Control) and the residuals remained, as assessed by the SPM model. For each group, bold line shows the median, central box includes the middle 50% of the data, and tails of the boxplot show the minimum and maximum values.</p

Localization of the atrophy.

<p>A. Schematic initial progression of Lewy body deposits in the first stages of Parkinson's Disease, as proposed by Braak and colleagues. B. Localization of the cluster of significant volume reduction in PD compared with HC. The significant cluster located in the medulla oblongata/pons is superimposed as a red blob on the mean normalized anatomical scan of all participants. The axial and sagital sections are centered on the peak of significance (−1; −36; −49).</p

Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission.

International audienc