Nigrostriatal dysfunction in homozygous and heterozygous parkin gene carriers: an 18F-dopa PET progression study.
Little is known about the rate of progression of striatal dysfunction in subjects with parkin-linked parkinsonism. Being a heterozygous parkin gene carrier may confer susceptibility to Parkinson's disease (PD). In a previous (18)F-dopa PET study, we reported that 69% of carriers of a single parkin mutation showed subclinical loss of putamen dopaminergic function. Using serial (18)F-dopa PET, the present longitudinal study addresses rates of progression of nigrostriatal dysfunction in both compound heterozygous (parkin-linked parkinsonism) and single heterozygous parkin gene carriers. Three symptomatic patients who were compound heterozygotes for parkin gene mutations and six asymptomatic heterozygous carriers were clinically assessed and had (18)F-dopa PET at baseline and again after 5 years. The patients with symptomatic parkin showed a mean 0.5% annual reduction in putamen (18)F-dopa uptake over 5 years while caudate (18)F-dopa uptake declined by a mean annual rate of 2 %. The asymptomatic heterozygote gene carriers showed a mean 0.56% annual reduction in putamen and 0.62 % annual reduction in caudate (18)F-dopa uptake. Neurological examination at both baseline and follow-up showed no evidence of parkinsonism. Loss of nigrostriatal dysfunction in parkin-linked parkinsonism occurs at a very slow rate compared to the 9-12% annual loss of putamen (18)F-dopa uptake reported for idiopathic PD. Although subclinical reductions of striatal (18)F-dopa uptake are common in carriers of a single parkin mutation their slow rate of progression suggests that few if any of these will develop clinical parkinsonism.
Pavese
Nicola
N
MRC Clinical Science Centre, Imperial College, London, United Kingdom. nicola.pavese@ csc.mrc.ac.uk
Khan
Naheed L
NL
Scherfler
Christoph
C
Cohen
Lisa
L
Brooks
David J
DJ
Wood
Nicholas W
NW
Bhatia
Kailash P
KP
Quinn
Niall P
NP
Lees
Andrew J
AJ
Piccini
Paola
P
D000368:Aged; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000187:drug effects; D005260:Female; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein