Nigrostriatal dysfunction in homozygous and heterozygous parkin gene carriers: An 18 F‐dopa PET progression study

• Published in: Movement disorders 2009-11, Vol.24 (15), p.2260-2266
• Main Authors: Pavese, Nicola, Khan, Naheed L., Scherfler, Christoph, Cohen, Lisa, Brooks, David J., Wood, Nicholas W., Bhatia, Kailash P., Quinn, Niall P., Lees, Andrew J., Piccini, Paola
• Format: Article
• Language: English
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.22817

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. © 2009 Movement Disorder Society