Pathological assessment of Lewy body disease (LBD) reveals aggregates of α-synuclein, referred to as Lewy bodies, found in neurons and glia. Their presence is required for the pathological diagnosis of LBD. Lewy bodies are present not only in the brain stem but also in the limbic system and neocortex in relation to their phenotypes. In addition to central nervous system involvement, variable amounts of Lewy body burden are found in the peripheral nervous system and autonomic nervous system (Wakabayashi and Takahashi 1997). A postmortem study reported cardiac plexus was more heavily involved than the sympathetic ganglia in patient with PD (Mitsui et al. 2006). On the other hand, other movement disorder and dementia syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), essential tremor, frontotemporal dementia, and Alzheimer’s-type dementia (AD), generally found no sympathetic ganglionic changes. Accordingly, Lewy body disease is not specific to the brain but instead is a generalized neuronal disorder.

PD, DLB and pure autonomic failure (PAF) are recognized as LBD. Among all neurological diseases, they are characterized by a significant reduction in MIBG uptake. Recently, a markedly reduced cardiac MIBG uptake was also reported in idiopathic rapid eye movement sleep behavior disorder (RBD), consistent with the loss of sympathetic terminals and suggesting an association of RBD with Lewy body pathology (Miyamoto et al. 2006) (Fig. 19.2). As ¹²³I-N-ω-fluoropropyl-2β- carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT) SPECT successfully visualizes presynaptic dopaminergic degeneration of the nigrostriatal tract, the finding of reduced tracer uptake in basal ganglia is recognized as a feature “suggestive” of DLB (Mckeith et al. 2005) (Table 19.2). A study aimed at differentiation of PD from atypical parkinsonian disorder revealed that ^123I-FP-CIT SPECT and MIBG scintigraphy have similar diagnostic accuracy (Südmeyer et al. 2011).

In general, a neurological differential diagnosis in the early stages between PD, MSA, PSP, and corticobasal degeneration (CBD) is important because of differences in prognosis and therapy among these diseases. In contrast with PD, central and preganglionic neurons are predominantly affected, while postganglionic neurons are usually spared in MSA. Therefore, cardiac MIBG uptake might not be impaired. In MSA, cardiac MIBG uptake is higher than that in PD, irrespective of the severity of autonomic dysfunction (Yoshita 1998; Braune et al. 1999; Orimo et al. 1999). Although 77–95 % discrimination specificity between PD and MSA has been proposed (Braune 2001; Treglia et al. 2011), the Quality Standards Subcommittee of the American Academy of Neurology found insufficient evidence to recommend MIBG cardiac imaging for differentiating PD from MSA (Suchowersky et al. 2006). A few cases of patient with MSA showed decreased cardiac MIBG uptake (Yoshita 1998, 2000). A small number of patients with MSA have postmortem evidence of postganglionic cardiac denervation which may account for the reported decreased cardiac MIBG uptake (Orimo et al. 2007). These cases of MSA may have involvement of both glial cytoplasmic inclusion in the brain and Lewy bodies in sympathetic ganglia.

PSP, classified as tauopathy, is a degenerative disorder causing supranuclear gaze palsy, bradykinesia, muscular rigidity with progressive axial dystonia, pseudobulbar palsy, and subcortical dementia. The H/M ratio of this disease entity is within normal range or slightly reduced (Yoshita 1998; Taki et al. 2000). However, we have noted a markedly low MIBG uptake in about 20 % of patients with PSP (Yoshita et al. 2008) (Table 19.4, Fig. 19.4). These cases of PSP may have concomitant Lewy bodies (Mori et al. 2002).