Jan Booij

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

To evaluate whether visual assessment of [123I]‐FP‐CIT (DaTSCAN , Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET).

Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study

BACKGROUND Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimers disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. METHODS We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025. FINDINGS Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimers disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohens kappa=0.87). The procedure was well tolerated with few adverse events. INTERPRETATION A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimers disease.

[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.

Gender differences in Parkinson's disease

Objective: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson’s disease (PD). Methods: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration ⩽10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson’s Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration ([123I]FP-CIT single photon emission computed tomography measurements). Results: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal [123I]FP-CIT binding than men at symptom onset and throughout the course of PD. Conclusions: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD.

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell

By the time a clinical diagnosis of Parkinsons disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]β‐CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, 2 of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I]β‐CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers.

Abstract.Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [123I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of ±110 MBq [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.

EANM procedure guidelines for PET brain imaging using [ 18 F]FDG, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose ([18F]FDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002 [1] and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations.

Memory disturbances in Ecstasy users are correlated with an altered brain serotonin neurotransmission

Abstract Rationale: Methylenedioxymethamphetamine (MDMA) is known to damage brain pre-synaptic serotonin (5-HT) neurons. Since loss of 5-HT neurons has been implicated in memory loss, it is important to establish whether MDMA use may produce changes in postsynaptic 5-HT receptors and memory function in humans. Objectives: To investigate whether MDMA use leads to compensative alterations in post-synaptic 5-HT2A receptors and whether there is a relation with memory disturbances. Methods: Brain cortical 5-HT2A receptor densities were studied with [123I]-5-I-R91150 SPECT in five abstinent MDMA users and nine healthy controls. Memory performance was assessed using RAVLT. Results: [123I]-5-I-R91150 binding ratios were significantly higher in the occipital cortex of MDMA users than in controls, indicating up-regulation. Mean cortical 5-HT2A receptor binding correlated positively with RAVLT-recall in MDMA users. Conclusion: Our preliminary results may indicate altered 5-HT neuronal function with correlated memory impairment in abstinent MDMA users.

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.