Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study.

Amanda Worker,Andrew Simmons,Camilla Blain,Flavio Dell’Acqua,Steve C R Williams,Richard G Brown,P Nigel Leigh,Jozef Jarosz,K Ray Chaudhuri,Gareth J Barker

doi:10.1371/journal.pone.0112638

Abstract

Although often clinically indistinguishable in the early stages, Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD.

Highlights

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that are characterized by very similar motor symptoms, making them difficult to distinguish in the early stages [1,2], despite having distinct molecular pathology [3,4,5]
Studies utilising fractional anisotropy (FA), mean diffusivity (MD) and other diffusion measures in PSP have described abnormalities in the superior longitudinal fasciculus, corpus callosum [12,13] and superior cerebellar peduncles [13,14,15,16,17], whilst in MSA white matter abnormalities have been identified in the putamen [8] and middle cerebellar peduncles [18,19]
Regions of increased MD were found in the PSP group in the corpus callosum, superior corona radiata, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, cerebral peduncle and posterior limb of the internal capsule bilaterally (Figure 1; Table 3)

Summary

Introduction

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that are characterized by very similar motor symptoms, making them difficult to distinguish in the early stages [1,2], despite having distinct molecular pathology [3,4,5].A range of Magnetic Resonance Imaging (MRI) techniques have been used to identify regions of brain pathology in parkinsonian syndromes. Previous imaging studies have highlighted pathological changes in white matter, with some involvement of the cortex [6,7,8,9,10]. Diffusion tensor imaging (DTI) provides an indirect insight into white matter microstructure in disease [11]. Studies utilising FA, MD and other diffusion measures in PSP have described abnormalities in the superior longitudinal fasciculus, corpus callosum [12,13] and superior cerebellar peduncles [13,14,15,16,17], whilst in MSA white matter abnormalities have been identified in the putamen [8] and middle cerebellar peduncles [18,19]. In non-demented PD, white matter is thought to remain largely normal [20], there have been reports of corpus callosum, superior cerebellar peduncles, cingulum and uncinate involvement [17]

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