A magnetic resonance imaging (MRI) study supports the hypothesis that degeneration occurs in the substantia nigra pars compacta (SNc) before the basal forebrain in patients with Parkinson's disease (PD).
"Our results provide in vivo evidence in support of the staging scheme by Braak et al, adding credence to their proposed rostral-to-caudal progression of pathological change," write David Ziegler (Massachusetts Institute of Technology, Cambridge, USA) and team.
The researchers used multiecho T1-weighted, multiecho proton density, T2-weighted, and T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI sequences. They found that combining the images to give a multispectral weighted mean for each patient gave "excellent contrast" for the SNc, whereas T2-weighted FLAIR imaging gave by far the best contrast for the basal forebrain, which was not further improved by adding data from other imaging sequences.
These techniques revealed substantially reduced SNc volumes on both sides in 13 patients with Hoehn and Yahr (H&Y) stage 1 PD relative to 27 age-matched healthy controls, at about 110 versus 145 mm3 for the left side, for example.
In the 16 patients with H&Y stage 2-3, average SNc volumes were only slightly smaller than in patients with H&Y stage 1. However, average basal forebrain volume was significantly reduced on both sides relative to that in both H&Y stage 1 patients and controls, at about 110 versus 125 mm3 on the left side.
"Although some aspects of the Braak neuropathological staging scheme remain a topic of debate and continued research, results from this study provide in vivo support for the Braak proposal of Lewy body pathological spread rostrally, affecting the SNc before the [basal forebrain]," say Ziegler et al in JAMA Neurology (formally Archives of Neurology).
They add: "A critical outstanding question is whether subgroups of patients exist who do not show this temporal progression of pathological change. If so, what are the frequencies and clinical ramifications?"
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