期刊
EXPERIMENTAL NEUROLOGY
卷 198, 期 2, 页码 450-456出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2005.12.021
关键词
difference image analysis; cerebellar lesions; VBM; longitudinal study; histogram analysis
资金
- NCRR NIH HHS [M01 RR02602] Funding Source: Medline
- NINDS NIH HHS [2 P50NS039787-06A] Funding Source: Medline
Background: A recent human therapeutic trial using intraputaminal infusion of glial cell-derived neurotrophic factor(GDNF) in Parkinson's disease (PD) was abruptly terminated, partly due to safety concerns raised by the finding of cerebellar lesions in monkeys given high-dose GDNF. Methods: Magnetic resonance images front nine PD patients participating in this trial were analyzed to determine whether Subtle volumetric or intensity changes could be detected in the cerebellum or elsewhere following GDNF treatment for over 1 year. Subtraction images were compared to a reference standard deviation map constructed by using identically-processed paired scans from 25 normal adults. In a separate voxel-based group morphometric (VBM) analysis of the same patient images, grey matter intensity was compared between pre and post-GDNF infusion scans using a repeated measures ANOVA with family-wise error threshold of P=0.10. Two expert readers independently reviewed serial FLAIR images from all patients. Results: (1) There were no significant cerebellar differences in any of the nine individual PD patients (difference image analysis), (2) there were no significant morphometric differences between pre- and post-GDNF scans (VBM), and (3) there were no signal abnormalities in the cerebellum detected on the FLAIR images in PD patients (clinical scan review). Conclusions: In concert with lack of evidence of cerebellar dysfunction on clinical examination, we find no imaging evidence of cerebellar injury in human subjects undergoing chronic intracerebral GDNF infusion. (C) 2005 Elsevier Inc. All rights reserved.
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