THE RELATIONSHIP BETWEEN LOCOMOTOR DISABILITY, AUTONOMIC DYSFUNCTION, AND THE INTEGRITY OF THE STRIATAL DOPAMINERGIC SYSTEM IN PATIENTS WITH MULTIPLE SYSTEM ATROPHY, PURE AUTONOMIC FAILURE, AND PARKINSON'S DISEASE, STUDIED WITH PET

Abstract

¹⁸F-dopa and S-¹¹C-nomifensine (NMF) are position emitting tracers whose caudate and putamen uptake reflects striatal dopamine stroage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with position emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar alaxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific ¹⁸F-dopa uptake into strialal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects [mean putamen Ki 0.005 min⁻¹ MSA vs 0.013 min⁻¹ controls; mean caudate Ki 0.007 min⁻¹ MSA vs 0.013 min⁻¹ controls]. Reduction of putamen, but not caudate, ¹⁸F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen ¹⁸F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate ¹⁸F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific strialal S-¹¹C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of strialal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostrital nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.