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

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.

Stereological Evaluation of the Brains in Patients with Parkinson’s disease Compared to Controls

“…This may be the first identifiable stage of the disease. In their patients the white matter gets atrophy by aging but there was no evidence of atrophy in gray and white matter of the brainstem (40). The results of the current study showed there were no significant differences in brainstem volumes between PD patients and control group.…”

Gray matter atrophy distinguishes between Parkinson disease motor subtypes

“…37,38 In addition, some reports showed no differences between PD and controls. 39,40 Differences in the relative representation of the PIGD and TD subtypes may explain the disparate findings in these earlier reports. Our findings highlight the need to distinguish among the clinical subtypes when investigating the neural correlates underlying PD.…”

A novel computerized algorithm to detect microstructural brainstem pathology in Parkinson’s disease using standard 3 Tesla MR imaging

“…Conventional and advanced MR studies have recently reported an involvement of the pontomedullary brainstem in PD [11,24,25], but also in other a-synuclein pathologies such as dementia with Lewy bodies or idiopathic rapid-eye-movement sleep disorder [26]. Jubault and colleagues [11] described a comparable pattern of brainstem abnormalities in 23 PD patients at Hoehn and Yahr stages I-II compared to healthy controls in a group level analysis that corresponds very closely to our results (peak significance in MNI space: -1, -36, -49; volume 4,287 mm 3 ).…”

“…The first study demonstrating in vivo that conventional T1-weighted MR imaging is able to detect white matter (WM) atrophy in the pontomedullary junction in mild-tomoderate PD was performed by Jubault and colleagues using voxel-based morphometry [11].…”