Elsevier

NeuroImage

Volume 21, Issue 4, April 2004, Pages 1443-1451
NeuroImage

Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease

https://doi.org/10.1016/j.neuroimage.2003.12.005Get rights and content

Abstract

We have recently shown that diffusion-weighted magnetic resonance (MR) imaging (DWI) discriminates patients with the Parkinson variant of multiple system atrophy (MSA-P) from those with Parkinson's disease (PD) by regional apparent diffusion coefficients (rADC) in the putamen. Because rADCs measured in one direction may underestimate diffusion-related pathologic processes, we investigated the diffusivity in different brain areas by trace of diffusion tensor (Trace(D)) in a new cohort of patients with MSA-P and PD. We studied 11 MSA-P, 17 PD patients, and 10 healthy volunteers matched for age and disease duration. Regional ADCs in three orthogonal directions and Trace(D) values were determined in selected brain regions including the basal ganglia, gray matter, white matter, substantia nigra, and pons. MSA-P patients had significantly higher putaminal and pallidal rTrace(D) values as well as rADCs in y- and z-direction than both PD patients and healthy volunteers. Moreover, putaminal Trace(D) discriminated completely MSA-P from both PD and healthy volunteers. The rADCs in the y- and z-direction provided a complete or near complete separation. In conclusion, our study confirms the results of previous studies of our group that patients with MSA-P show an increased putaminal diffusivity due to neuronal loss and gliosis. Because rADCs in one direction are dependent on the slice orientation relative to the directions of fiber tracts, Trace(D) imaging appears to be more accurate in the separation of MSA-P from PD.

Introduction

The differential diagnosis of parkinsonian disorders means a challenge for clinicians, especially during the early stages of disease (Poewe, 1993). The differentiation of Parkinson's disease (PD) from the parkinsonian variant of multiple system atrophy (MSA) carries a high rate of misdiagnosis (Wenning et al., 1997). MSA is a sporadic, progressive, adult-onset neurodegenerative disorder associated with varying degrees of parkinsonism, autonomic dysfunction, and cerebellar ataxia. Neuropathologically, the Parkinson variant of MSA (striatonigral degeneration (SND) type, MSA-P) is characterized by selective neuronal loss and gliosis predominantly affecting the basal ganglia, substantia nigra, olivopontocerebellar pathways, and the intermediolateral cell column of the spinal cord (Wenning et al., 1997). An early differentiation between PD and MSA-P has important prognostic and therapeutic implications Lang and Lozano, 1998a, Lang and Lozano, 1998b, Quinn and Marsden, 1993, Redmond et al., 1990, Spencer et al., 1992.

Routine, spectroscopic, and volumetric magnetic resonance imaging (MRI) may be helpful in the differential diagnosis of MSA-P vs. PD; however, both sensitivity and specificity of reported MR indices are generally suboptimal Bhattacharya et al., 2002, Davie et al., 1995, Federico et al., 1997, Kraft et al., 1999, Kraft et al., 2002, Litvan, 1999, Schrag et al., 1998, Schulz et al., 1999. A recent diffusion-weighted MRI (DWI) study by our group reported complete separation of patients with MSA-P from patients with PD (Schocke et al., 2002). In this study, the apparent diffusion coefficients (ADC) measured in z-direction were determined for several brain regions. DWI provided a full discrimination of patients with MSA-P and PD as well as normal controls by putaminal ADCs (Schocke et al., 2002).

Because the central nervous system (CNS) is organized in bundles of fiber tracts, the water molecules mainly move along these structures, whereas diffusion perpendicular to the fiber tracts is restricted (Hajnal et al., 1991). DWI only measured in one direction can lead to an underestimation of diffusion-related pathological changes because the fiber tracts are not orientated in the same direction (Pierpaoli et al., 1996). The trace of diffusion tensor Trace(D) is given by the average of ADCs measured in three orthogonal directions and is by definition independent of anisotropy (Hsu and Mori, 1995). Therefore, evaluation of Trace(D) appears to be more sensitive than ADCs measured in only one direction. We applied here mapping of Trace(D) to patients with MSA-P and PD as well as normal controls to obtain additional information about diffusion-related processes.

Section snippets

Patients

We included 10 consecutive patients with probable MSA-P (Gilman et al., 1998) and 17 consecutive patients with PD (Hughes et al., 1992) matched for age, disease duration, and Hoehn and Yahr “off” stage who were recruited at the Parkinson outpatient clinic. Clinical diagnosis of probable MSA-P and PD was made according to the established criteria Gilman et al., 1998, Hughes et al., 1992 by one of our movement disorder specialists experienced in parkinsonian disorders (G.K.W., W.P.). A detailed

Patients

The clinical and demographic data of the patients and normal controls are given in Table 1. Patients' age was not significantly different between groups at the time of MRI examination. Mean age at examination was 62 (±8.0, standard deviation) years in PD patients, 64 (±5.8) years in MSA-P patients, and 60 (±5.8) years in healthy volunteers. There were no significant differences in disease duration of patients with PD (3.7 ± 1.8 years) and patients with MSA-P (3.9 ± 1.9 years). There was no

Discussion

Because the differential diagnosis between MSA-P and PD is difficult in early stages of disease, several neuroimaging methods have been previously evaluated for the differentiation of MSA from other parkinsonian disorders, in particular PD. A systematic analysis of routine MRI in MSA patients reported alterations such as hyperintensive putaminal rim, putaminal atrophy, and hyperintensive putamen (Schrag et al., 1998). However, a substantial minority of patients fulfilling the diagnostic

Acknowledgements

The study was supported by the Austrian Federal Ministry of Science and Transport (GZ 70038/2 PR 4/98).

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