Asymmetrical pre-synaptic and post-synpatic changes in the striatal dopamine projection in dopa naïve parkinsonism. Diagnostic implications of the D2 receptor status.
Nine L-dopa na ve patients with clinically diagnosed parkinsonism were studied using positron emission tomography with 6-L-[18F]fluorodopa ([18F]dopa, a pre-synaptic tracer) and [11C]raclopride (which binds to D2 receptors). Putamen [18F]dopa uptake was reduced in all patients, confirming a loss of function affecting the nigrostriatal projection. In eight patients the putamen with the lowest [18F]dopa uptake (always contralateral to the clinically most affected side) had the highest [11C]raclopride binding, suggesting upregulation of the post-synaptic D2 receptors. In the ninth patient [11C]raclopride binding was lower in the putamen with the lowest [18F]dopa uptake, indicating an additional post-synaptic deficit. All nine patients were shown to be L-dopa responsive. The subsequent clinical course of the former eight patients has been typical of idiopathic Parkinson's disease, whilst the ninth patient has developed postural hypotension, urinary incontinence and respiratory stridor typical of multiple system atrophy. Reduced [11C]raclopride binding in L-dopa naïve parkinsonian patients might serve as a useful early marker of this condition.
Sawle
G V
GV
Clinical Sciences Section, Hammersmith Hospital, London, UK.
Playford
E D
ED
Brooks
D J
DJ
Quinn
N
N
Frackowiak
R S
RS
D000328:Adult; D000368:Aged; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D004295:Dihydroxyphenylalanine; D004298:Dopamine