G. Tissingh

[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

OBJECTIVES: The main neuropathological feature in Parkinsons disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinsons disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinsons disease, using a one day protocol. METHODS: [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinsons disease, and in six age matched healthy volunteers. RESULTS: Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinsons disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinsons disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinsons disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinsons disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls. CONCLUSION: [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinsons disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.

Loss of olfaction in de novo and treated Parkinson's disease: Possible implications for early diagnosis

Olfactory dysfunction is a common finding in patients with Parkinsons disease (PD). As most studies reported on odor identification in more advanced and treated PD, we administered an odor detection, discrimination, and identification test to a heterogeneous, partly de novo, group of patients. Forty‐one non‐demented PD patients, 24 of whom had untreated early PD, and 18 healthy controls, were examined. Odor identification and discrimination data were corrected for odor detection scores. PD patients scored significantly lower on all olfactory tests. Interestingly, the subgroup of de novo patients with early PD also showed significant olfactory disturbances compared with healthy subjects. Within the PD group, using multiple regression analysis, we found a significant, negative correlation between odor discrimination measures and disease severity.

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Abstract. Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.

Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT

Abstract Ten healthy subjects and 16 patients with early Parkinson’s disease (PD) were examined with single photon emission computed tomography (SPECT) and [123I]β-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [123I]β-CIT binding in the ipsi- and contralateral striatal regions, especially in the putamen, which showed a mean reduction of 65% of the control mean. Discriminant function analysis of the putaminal [123I]β-CIT binding measures classified 100% of the cases in the correct group. Disease severity correlated negatively and highly significantly with the binding measures. Tremor ratings did not correlate with the SPECT measures, whereas rigidity, and to a lesser extent bradykinesia, did. Patients with unilateral PD showed a bilateral loss of striatal DA transporters. Our findings indicate that with [123I]β-CIT SPECT it is possible to diagnose PD in subjects with very mild symptoms and signs. Moreover, finding a bilateral loss of striatal DA transporters in patients with unilateral PD also suggests that it may be possible to identify subjects in the preclinical phase of the disease.

Practical benefit of [123I]FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson's disease

Loss of striatal dopamine (DA) transporters in Parkinsons disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [123I]β-CIT. However, these studies have also shown that adequate imaging of the striatal DA transporter content can be performed only 20–30 h following the injection of [123I]β-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand,N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)tropane (FP-CIT), became available for in vivo imaging of the DA transporter. The faster kinetics of [123I]FP-CIT have been shown to allow adequate acquisition as early as 3 h following injection. In the present study, loss of striatal DA transporters in five non-medicated PD patients was assessed on two consecutive SPET scans, one with [123I]β-CIT (24 h following injection) and one with [123I]FP-CIT (3 h following injection). The ratios of specific to non-specific [123I]FP-CIT uptake in the caudate nucleus and putamen were consistently 2.5-fold lower than those of [123I]β-CIT. However, when the uptake ratio of both ligands in these brain regions of patients was expressed as a percentage of the uptake ratio found in healthy controls, both the decrease and the variation of the data were similar. It is concluded on the basis of these findings that [123I]FP-CIT seems as good as [123I]β-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [123I]FP-CIT are a clear advantage.

Dopamine agonists in Parkinson's disease

The main pathologic hallmark of Parkinsons disease is a degeneration of the dopaminergic cells in the substantia nigra, pars compacta and-to a lesser extent--in the ventral tegmental area. Striatal dopamine concentrations are significantly reduced before clinical symptoms become apparent. Recent neuroanatomic and function studies have revealed that the nigrostriatal dopaminergic projection is only one of the neuronal elements integrated into extensive basal ganglia-thalamocortical circuits that are intimately involved in the regulation of motor activity. The possibilities for therapeutic intervention at the level of the different dopamine receptor subtypes and their effect on the regulation of motor behavior will be briefly reviewed. Dopamine precursors are considered to provide the best symptomatic treatment, whereas dopamine agonists, although less effective, might be important in slowing the progression of the disease. Our results with pergolide as monotherapy and in combination therapy in patients with Parkinsons disease also are discussed. NEUROLOGY 1995;45(suppl 3): S28-S34

[123I]β-CIT single-photon emission tomography in Parkinson's disease reveals a smaller decline in dopamine transporters with age than in controls

In vivo studies using single-photon emission tomography (SPET) and positron emission tomography have shown an age-related decline in the number of striatal dopamine transporters in healthy subjects. We examined ten healthy subjects and 33 de novo patients with Parkinsons disease (PD) using [123I]2β-carbomethoxy-3β-(4-iodophenyl)tropane ([123I]β-CIT) SPET. A clear age-related loss of dopamine transporters was found in the healthy subjects. In the PD group, controlling for the contribution of disease severity, we found a small (compared with controls) but significant decrease with aging, though only in the ipsilateral regions. This aging effect was especially pronounced in younger patients. We conclude that the use of age-correct SPET data in PD, based on studies with healthy subjects, may lead to an underor an overestimation of the striatal binding measures.

Evaluation of [123I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinsons disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.

Sporadic Creutzfeldt-Jakob disease in a young Dutch valine homozygote: Atypical molecular phenotype

A case of sporadic Creutzfeldt‐Jakob disease (sCJD) is described in a young Dutch protein prion gene (PRNP) codon 129 valine homozygote. Certain clinical and molecular features of this case overlap those of variant CJD. The case highlights possible difficulties in the differential diagnosis of vCJD and the more rare sCJD subtypes based on molecular features alone.

rCBF SPECT in Parkinson’s disease patients with mental dysfunction

Functional imaging of the brain using SPECT provides information correlative to the alterations of regional blood flow. In this paper we review the literature pertaining to SPECT in Parkinsons disease with and without dementia and depression. Parkinsons disease itself is not associated with a consistent pattern of cerebral blood flow alterations in the basal ganglia, but reduced parietal blood flow is more often reported. The heterogeneity of blood flow changes possibly reflects the multifactorial pathophysiology of the disease. In demented Parkinsons disease patients frontal hypoperfusion is often found or bilateral temporoparietal deficits, probably indicative of concomitant Alzheimers disease. The SPECT studies undertaken in depressed patients with and without Parkinsons disease show highly conflicting and inconsistent results, probably due to methodological and diagnostic flaws (especially the inclusion of demented Parkinson patients). Several lines of reasoning point to a prefrontal dysfunction and future SPECT studies are planned to study this region in non-demented Parkinsons disease patients with and without major depression.