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Abstract
Objective: Multiple system atrophy (MSA), the most common of the atypical parkinsonian disorders, is characterized by the presence of an abnormal spatial covariance pattern in resting state metabolic brain images from patients with this disease. Nonetheless, the potential utility of this pattern as a MSA biomarker is contingent upon its specificity for this disorder and its relationship to clinical disability in individual patients.
Methods: We used [18F]fluorodeoxyglucose PET to study 33 patients with MSA, 20 age- and severity-matched patients with idiopathic Parkinson disease (PD), and 15 healthy volunteers. For each subject, we computed the expression of the previously characterized metabolic covariance patterns for MSA and PD (termed MSARP and PDRP, respectively) on a prospective single-case basis. The resulting network values for the individual patients were correlated with clinical motor ratings and disease duration.
Results: In the MSA group, disease-related pattern (MSARP) values were elevated relative to the control and PD groups (p < 0.001 for both comparisons). In this group, MSARP values correlated with clinical ratings of motor disability (r = 0.57, p = 0.0008) and with disease duration (r = −0.376, p = 0.03). By contrast, MSARP expression in the PD group did not differ from control values (p = 1.0). In this group, motor ratings correlated with PDRP (r = 0.60, p = 0.006) but not with MSARP values (p = 0.88).
Conclusions: MSA is associated with elevated expression of a specific disease-related metabolic pattern. Moreover, differences in the expression of this pattern in patients with MSA correlate with clinical disability. The findings suggest that the MSARP may be a useful biomarker in trials of new therapies for this disorder.
GLOSSARY
- FDG=
- [18F]fluorodeoxyglucose;
- MNI=
- Montreal Neurological Institute;
- MSA=
- multiple system atrophy;
- MSA-C=
- multiple system atrophy cerebellar subtype;
- MSA-P=
- multiple system atrophy parkinsonian subtype;
- MSARP=
- multiple system atrophy–related spatial covariance pattern;
- PDRP=
- Parkinson disease–related spatial covariance pattern;
- PD=
- Parkinson disease;
- ROI=
- region of interest;
- SPM=
- Statistical Parametric Mapping;
- UPDRS=
- Unified Parkinson's Disease Rating Scale
Footnotes
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Study funding: Supported by the NIH (NINDS R01 NS 35069 and P50 NS 071675) to D.E. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIH.
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Supplemental data at www.neurology.org
- Received July 15, 2011.
- Accepted December 8, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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