Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson's disease

Abstract

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) provide the means to studying in vivo the neurochemical, hemodynamic or metabolic consequences of the degeneration of the nigrostriatal dopaminergic system in Parkinson's disease (PD). The extent of striatal dopaminergic denervation can be quantified with radiotracers as [18F]FDopa for PET and [123I]tropanes for SPECT. There are other radiotracers such as [11C]Dopa and meta-tyrosines as well as PET tracers for uptake sites. Striatal uptake of [18F]FDopa and [123I]tropanes is markedly decreased in PD, more in the putamen than in the caudate nucleus, and inversely correlates with the severity of motor signs and with duration of disease. PET and SPECT make possible the assessment by noninvasive means of the changes in dopamine receptor density, the effect of neuronal transplants or neuroprotective treatments in PD patients, or the nigrostriatal dopaminergic function in at-risk subjects. Activation studies using cerebral blood flow and metabolism measurements during a motor task reveal an impaired ability to activate the supplementary motor area and dorsolateral prefrontal cortex in PD. This functional disability is reversed by the use of dopaminergic medication or by surgical treatment by pallidotomy or deep brain stimulation. The differential diagnosis between PD and multiple system atrophy, progressive supranuclear palsy or corticobasal degeneration is not yet clearly established by PET and SPECT, even though these syndromes have some particular neurochemical and metabolic profiles. On the other hand, PET and SPECT are useful for distinguishing PD from Dopa-responsive dystonia, or for assessing the integrity of the nigrostriatal dopaminergic pathway in atypical cases of postural tremor or iatrogenic parkinsonian syndromes.