Thomas Jubault; Simona M. Brambati; Clotilde Degroot; Benoît Kullmann; Antonio P. Strafella; Anne-Louise Lafontaine; Sylvain Chouinard; Oury Monchi

“ Lewy bodies have been historically considered as the hallmark of the disease [25] , and more recently, their presence in the substantia nigra has been proposed to correlate with the motor scores of the UPDRS [26] . However, recent progresses in molecular biology and histo-immunology suggest that alpha-synuclein deposits, which constitute the main part of Lewy bodies, involve other cerebral structures than those latter, including the pons and the medulla oblongata, and that it should be considered as a more direct measure of PD pathology and clinical symptomatology [27] . ”

“ In the framework of Braak's progression of the disease, we should observe damages across all PD patients localized in the brainstem, the hypothesized initial location of the neurodegeneration. Voxel based morphometry (VBM) is a technique that identifies local atrophies without the subjective selection of an a priori region of interest. Based on previous neuropathological findings, we expected to observe brain tissue volume reduction in the medulla oblongata/lower pontine tegmentum of PD patients compared to healthy control subjects. ”

“ PD clinical diagnosis is particularly prone to errors [1] , [2] , as this array of motor symptoms is also present in a wide range of other parkinsonian conditions such as progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy. Confirmation of the diagnosis is often brought by disease progression and the response of patients to levodopa medication. ”

“ The key result is the finding of a single significant cluster of white matter volume reduction, overlapping the rostral part of the medulla oblongata and the caudal part of the pons. This finding is consistent with the existence of a common anatomical starting point of PD, in accordance with Braak et al. [10] , [12] , unrelated to the duration of the disease, or the severity in term of motor impairments. This finding is also independent of age, although this factor is known to interact with PD condition [22] . ”

“ 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. We ran additional analyses to assess the effect of age in the tested population. No cluster of significant atrophy survived at the threshold used. At last, we ran analyses specific to the PD groups, using age, gender, UPDRS-III score and duration of the disease (expressed as the time elapsed between the first neurological diagnosis and the MRI acquisition) as covariates, and found no atrophy patterns. ”

“ 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. ”