123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: A systematic review and meta-analysis

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Abstract

Objectives

Differential diagnosis of Parkinson’s disease (PD) and other neurodegenerative parkinsonism by clinical consensus criteria and diagnostic imaging is often difficult. 123I-meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy is a useful imaging tool for differentiating PD from other parkinsonism. The purpose of the present study is to systematically review and perform a meta-analysis of studies on the diagnostic performance of 123I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism, specifically multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration.

Methods

A computer literature search of the PubMED/MEDLINE database was conducted to find relevant published articles on 123I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism. We used the bivariate random-effects model to obtain the pooled estimates of the sensitivity and specificity and the corresponding 95% confidence intervals.

Results

Thirteen studies comprising 845 patients including 625 PD and 220 other neurodegenerative parkinsonism were analyzed. The pooled sensitivity and specificity to differentiate PD from other neurodegenerative parkinsonism by the early heart-to-mediastinum (H/M) ratio were 82.6% and 89.2%, respectively, and those by the delayed H/M ratio were 89.7% and 82.6%, respectively. When PD was limited to early stage (Hoehn-Yahr stage 1 or 2), the pooled sensitivity and specificity by the delayed H/M ratio were 94.1% and 80.2%, respectively.

Conclusions

The present meta-analysis confirmed high sensitivity and specificity of 123I-MIBG myocardial scintigraphy for differentiating PD from other neurodegenerative parkinsonism in both early and delayed imaging phases. Furthermore, 123I-MIBG myocardial scintigraphy was highly effective for distinguishing early PD.

Introduction

Meta-iodobenzylguanidine (MIBG) is an analog of guanethidine, an adrenergic blocking agent, and its mechanism of uptake and storage is similar to that of noradrenaline. It is actively taken up by the postganglionic presynaptic nerve endings of the adrenergic nervous system by the energy-dependent noradrenaline transporter mechanism and is actively taken up by the noradrenaline vesicles by the ATPase-dependent proton pump via the vesicle monoamine transporter. Therefore, MIBG radiolabeled with iodine-123 (123I-MIBG) myocardial scintigraphy can non-invasively assess the postganglionic presynaptic cardiac sympathetic nerve endings. After intravenous injection of 123I-MIBG, planar and single photon emission computed tomography (SPECT) images of the chest are obtained using a gamma camera at 15–30 min (the early imaging phase) and at 3–4 h (the delayed imaging phase) post-injection. Cardiac MIBG uptake in the early imaging phase mainly reflects the density of the presynaptic cardiac sympathetic nerve endings, whereas the delayed imaging phase reflects the presynaptic functional tone of the cardiac sympathetic nerve as well. The uptake can be semi-quantitatively evaluated by calculating the heart-to-mediastinum (H/M) ratio by setting regions of interest over the heart and the upper mediastinum on the anterior planar view of the chest.

Parkinson’s disease (PD) is the most common neurodegenerative parkinsonism characterized by the degeneration of both dopaminergic and non-dopaminergic neurons with neuronal intracytoplasmic inclusion known as Lewy bodies. Despite the presence of consensus diagnostic criteria for PD and other neurodegenerative parkinsonism such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD), an accurate diagnosis of these disorders remains a challenge for neurologists. Differentiating PD from other neurodegenerative parkinsonism is difficult particularly in the early stage. However, the prognosis is completely different among these disorders, and the choice of treatment strategy becomes very important. Because early differentiation of PD and other neurodegenerative parkinsonism is crucial, there is an important need to improve the diagnostic accuracy.

123I-MIBG myocardial scintigraphy was originally developed to assess postganglionic presynaptic cardiac sympathetic nerve endings in heart diseases including congestive heart failure, ischemic heart disease, and cardiomyopathy. Subsequently, cardiac MIBG uptake was demonstrated to be reduced in patients with Lewy body diseases such as PD [1], [2] and dementia with Lewy bodies (DLB) [3] and has been reported to be useful for differentiating PD from other parkinsonism, as well as DLB from Alzheimer’s disease (AD). Postmortem studies have shown that the number of tyrosine hydroxylase (TH)-immunoreactive (ir) axons, a marker for sympathetic axons, of the heart was decreased in pathologically confirmed PD and DLB [4], [5] and supported the findings of reduced cardiac MIBG uptake in Lewy body diseases. There are many studies reporting the significance of 123I-MIBG myocardial scintigraphy for differentiating PD from other parkinsonism and essential tremor (ET), however, most were conducted in a single center with a relatively small number of patients and thus have limited power.

The purpose of the present study is to systematically review and perform a meta-analysis of studies on the diagnostic performance of 123I-MIBG myocardial scintigraphy for differentiating PD from other neurodegenerative parkinsonism, particularly MSA, PSP, and CBD, in both delayed and early imaging phases. Furthermore, we focused on the potential usefulness of 123I-MIBG myocardial scintigraphy in early PD.

Section snippets

Systematic review

A computer literature search of the PubMED/MEDLINE database was conducted to find relevant published articles on 123I-MIBG myocardial scintigraphy for the diagnosis of PD, MSA, PSP, and CBD. The following combination of search terms was used: (a) 3-iodobenzylguanidine, mibg, metaiodobenzylguanidine, or iobenguane, and (b) parkinson disease, parkinson, parkinsonism, parkinsonian, or lewy, (c) multiple system atrophy, (d) progressive supranuclear palsy, or (e) corticobasal degeneration. The

Systematic review

A total of 214 articles were obtained by the computer literature search. Of the 214 articles, 84 were excluded by the title and abstract screening: 12 were not in English or Japanese; 4 were retracted publications; 1 was an erratum; 4 were non-clinical studies; 39 were on non-parkinsonism topics such as dementia and rapid eye movement sleep behavior disorder (RBD); 12 were on familial or genetic parkinsonism; and 12 were case reports. The remaining articles were reviewed in full text, and 117

Discussion

Recently, a meta-analysis of 123I-MIBG myocardial scintigraphy on the differential diagnosis of Lewy body related disorders such as PD, DLB, and RBD was published and indicated 123I-MIBG myocardial scintigraphy is useful for differentiating Lewy body related diseases from non-Lewy body related diseases including AD, PSP, MSA, vascular dementia, and frontotemporal dementia [19]. This study did not evaluate pooled sensitivity and specificity and meta-analyzed only the delayed H/M ratio. Another

Acknowledgments

We would like to thank HS, MT, and YK for their work on this study.

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