Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm

Abstract

The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine ¹²³I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency. There is evidence to support an algorithm utilizing a dual neuroimaging strategy combining ¹²³I-ioflupane SPECT and the noradrenergic receptor ligand ¹²³I-metaiodobenzylguanidine (MIBG), which assesses the post-ganglion peripheral autonomic nervous system. Evolving concepts regarding the synucleinopathy affecting the central and peripheral autonomic nervous systems as part of a multisystem disease are reviewed to sustain such strategy. Data are presented to show how MIBG deficits are a common feature of multisystem Lewy body disease and can be used as a unique feature to distinguish PD from atypical parkinsonisms. We propose that the combination of cardiac (MIBG) and cerebral ¹²³I-ioflupane SPECT could satisfy one of the most significant unmet needs of current PD diagnosis and management, namely the early and accurate diagnosis of patients with typical Lewy body PD. Exemplary case scenarios will be described, highlighting how dual neuroimaging strategy can maximize diagnostic accuracy for patient care, clinical trials, pre-symptomatic PD screening, and special cases provided by specific genetic mutations associated with PD.

Fig. 1

MIBG-DAT dual imaging diagnostic algorithm. MIBG abnormality separates multisystem Lewy body disease (MLBD) pathologies, including idiopathic Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) from other types of parkinsonism. ¹²³I-Ioflupane measures the integrity of nigrostriatal dopamine projections. Low dopamine transporter (DAT) levels in the caudate, putamen or both, in either brain hemisphere, are consistent with a parkinsonian disorder, independently of its nature. In subjects with appropriate symptoms and signs, the combination of the two imaging modalities allows discriminating four distinct pathologies: (1) non-parkinsonian disorders (upper left quadrant, dual test normality); (2) atypical non-Lewy body parkinsonism (upper right quadrant, normal MIBG, and abnormal DAT); (3) early-stage MLBD or pre-symptomatic parkinsonism (lower left quadrant, abnormal MIBG and normal DAT); (4) MLBD, either DLB or PD (lower right quadrant, abnormal MIBG, and DAT)