Clinical Study
Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes

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Abstract

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa = 0.229, p = 0.074) but was 90.2% (kappa = 0.782, p < 0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.

Introduction

The diagnosis of parkinsonism is currently based on clinical evaluation, although the clinical signs may be related to a neurodegenerative disorder such as Parkinson’s disease (PD), progressive supranuclear palsy or multiple system atrophy.1 However, subtle parkinsonian signs are common in elderly patients with non-neurodegenerative disorders such as essential tremor.2

In general practice the presence of parkinsonism is misdiagnosed in up to a quarter of cases. According to Hughes et al., movement disorder specialists misdiagnose parkinsonian syndromes in up to 10% of cases. Histopathological findings are the “gold standard”, and the highest accuracy of PD diagnosis using the current clinical criteria is about 90%.3, 4 In another report, experienced neurologists were found to have altered their diagnosis in 36% to 54% of cases following the first evaluation.5 Additionally, in a considerable number of clinicopathological studies, a significant percentage of patients (10–25%) with an ante-mortem clinical diagnosis of PD were found to have other diseases in a post-mortem evaluation.6, 7

Although the differential diagnosis of PD from essential tremor or other parkinsonian syndromes is relatively straightforward according to the United Kingdom Parkinson’s Disease Society Brain Bank criteria, the diagnosis may be difficult in elderly patients or when the disorder is at an early stage and a false diagnosis is possible.8, 9, 10, 11, 12, 13

Therefore, new techniques to further improve the accuracy of diagnosing PD and other neurodegenerative parkinsonian syndromes early in the clinical course would be important and valuable tools for the clinician.

Dopamine transporter (DAT) is expressed exclusively on the presynaptic terminals of dopaminergic neurons. Degeneration of these terminals is accelerated in neurodegenerative parkinsonism, resulting in a reduction of the numbers of dopamine transporters. Imaging of presynaptic dopaminergic neurotransmission using radionuclide studies has become of significant clinical importance, not only for the objective confirmation of presynaptic nigrostriatal degeneration, but also for the early differential diagnosis of PD from non-neurodegenerative disorders.5

Several radiopharmaceuticals that have been developed for single photon emission computed tomography (SPECT) imaging can be used as sensitive and objective presynaptic dopaminergic markers. Among them, I-123 ioflupane (I-123 FP-CIT, DaTSCAN, General Electric Healthcare Division, Buckinghamshire, UK) is one of the most promising radiotracers, as it has favourable pharmacokinetic properties which allow imaging 3–6 hours post injection.14 SPECT imaging using I-123 ioflupane can accurately differentiate parkinsonian syndromes.5, 15

The aim of the present study was to assess the impact of I-123 ioflupane SPECT imaging on the classification of patients with striatal dopaminergic deficits and to evaluate its clinical application by the neurologists.

Section snippets

Patients

A total of 83 patients underwent a screening evaluation, of whom 22 patients were excluded (13 refused to sign the informed consent form and 9 were excluded because they did not fulfil the enrolment criteria). Finally, 61 Caucasian patients, aged 64.73 ± 13.60 years, were enrolled in the study, who had a mean duration of diagnosed illness of 4.36 ± 3.76 years (demographic and drug therapy data are summarised in Table 1). Twenty healthy volunteers were evaluated in order to obtain reference SPECT

Results

In the neurodegenerative group of patients (A1) the mean duration of the disease was 3.2 ± 2.8 years while in the non-neurodegenerative group (A2) the mean disease duration was 7.2 ± 4.7 years (Table 1). The diagnoses are presented in Table 2.

Forty patients (65.6%) were initially classified as having neurodegenerative parkinsonian disorders; for 8 of them (20.0%) the diagnosis was altered by our centre’s neurologists. Furthermore, among the 21 patients (34.4%) initially diagnosed as having

Discussion

According to our results, diagnoses based on SPECT imaging with I-123 ioflupane were in agreement with the diagnosis of the community’s neurologists in only 65.6% of patients. The concordance between the diagnoses of our centre’s neurologists and diagnoses based on SPECT imaging increased significantly to 90.2% of patients. Discordance in the diagnosis for 9.8% of patients resulted in re-evaluation of their diagnosis. Our results are in accordance with the data provided in other publications.

Conclusion and clinical implications

In conclusion, our results suggest that patients with a parkinsonian disorder should be evaluated in a specialised movement disorders centre and potentially undergo SPECT imaging of presynaptic dopaminergic neurotransmission if there is difficulty in differentiating parkinsonian from non-parkinsonian syndromes, as this provides objective confirmation of presynaptic nigrostriatal degeneration and contributes to the early diagnosis of neurodegenerative extrapyramidal disorders. However, SPECT

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