Nigral degeneration and striatal dopaminergic dysfunction in idiopathic and Parkin-linked Parkinson's disease.
We have used MR segmented inversion recovery ratio imaging (SIRRIM) of the substantia nigra pars compacta to detect and correlate nigral signal change in idiopathic Parkinson's disease (PD) and parkin patients with striatal (18)F-dopa uptake. Nine PD patients, nine parkin patients, and eight control subjects were studied with a combination of MR inversion recovery sequences sensitive to nigral cell loss. Blinded independent observer rating and quantified nigral signal analysis were performed on all subjects. Striatal regions of interest were defined on T(1)-weighted MRI co-registered to (18)F-dopa positron emission tomography. On blinded observer rating of the SIRRIM dorsal and ventral nigral images, 25% (2/8) of control subjects, 44% (4/9) of PD patients, and 67% (6/9) of parkin patients were classified as abnormal. Quantified total nigral signal intensities were reduced to a greater extent in the parkin compared to PD patients. There was a greater predilection for signal reduction in the ventral nigral slice of the PD compared to the parkin patient group, who showed a more uniform involvement. All PD and parkin patients were discriminated from controls on the basis of caudate and putamen (18)F-dopa Ki reductions. Our results suggest that MR segmented inversion recovery ratio imaging shows poor sensitivity for discriminating parkin and idiopathic PD patients from normal controls. Where nigral signal abnormalities were seen, parkin patients manifested generalized nigral cell loss with widespread striatal dopamine terminal dysfunction compared with the lateral nigral targeting seen in PD and selective loss of putamen (18)F-dopa uptake.
Hu
Michele T M
MT
MRC Clinical Sciences Centre, Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom.
Scherfler
Christoph
C
Khan
Naheed L
NL
Hajnal
Jo V
JV
Lees
Andrew J
AJ
Quinn
Niall
N
Wood
Nicholas W
NW
Brooks
David J
DJ
D000328:Adult; D002421:Caudate Nucleus / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation / Q000235:genetics; D049268:Positron-Emission Tomography; D011699:Putamen / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D004298:Dopamine