INTRODUCTION

Since ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy was approved by the Health and Welfare Ministry of Japan in 1992 [1], MIBG has typically been used to study the regional denervation of the heart in ischemic heart diseases, such as acute coronary syndromes and cardiomyopathies [2-5]. In the mid- 1990s, clinical trials of MIBG began in the field of neurology [6-12], and many countries have since begun to use MIBG scintigraphy to study related movement disorders and dementia [1].

MIBG scintigraphy is a diagnostic technique that is used to detect and evaluate sympathetic denervation [13]. In the last few years, MIBG scintigraphy has been reported as a useful tool for diagnosing Parkinson’s disease (PD) [9] and differentiating PD from other parkinsonisms, such as multiple system atrophy (MSA) [12], progressive supranuclear palsy (PSP) [8], vascular parkinsonism and drug-induced parkinsonism [14,15], and even from essential tremor [16]. Recently, MIBG scintigraphy has been used to discriminate dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) [17] and to predict the conversion to probable DLB [18]. Therefore, it is necessary to organize the scattered comprehensive MIBG studies on neurodegenerative disorders. The first purpose of this study is to systematically review the diagnostic application of MIBG scintigraphy in neurodegenerative disorders. Additionally, we investigate the potential usefulness of MIBG scintigraphy for the early detection, prognostic prediction and differentiation of various neurodegenerative disorders.

Neuroanatomy of sympathetic innervation

Sympathetic innervation of the heart originates in the intermediolateral column of the thoracic spinal cord, segments 1 to 5 [19]. The first synapses form in the upper-most thoracic and cervical ganglia [19]. Postganglionic noradrenergic sympathetic fibers accompany the blood vessels to the heart and enter into the myocardium [20,21].

Fundamentals of MIBG scintigraphy

MIBG is a pharmacologically inactive urea derivative that, like noradrenaline, is taken up by adrenergic cells via the human norepinephrine transporter mechanism, stored in vesicles, and secreted in response to a variety of stimuli [19,22-25]. Guanethidine may be chemically modified to MIBG [26-28]. MIBG can be labeled with radioactive iodine (most commonly ¹²³Iodine) to become ¹²³I-MIBG, and it is taken up by the postganglionic, presynaptic nerve endings [1,5,26-28]. Radiolabeled MIBG is considered an established sympathetic neuron imaging agent that is useful to study organs that are richly innervated by the sympathetic nervous system [1,5,27,28]. After depolarization, MIBG is released into the synaptic cleft, similar to norepinephrine, but it is not metabolized [1,5,27,28]. ¹²³I-MIBG uptake has been shown to correlate with adrenergic innervation [1,5,27]. Therefore, ¹²³I-MIBG scintigraphy reveals not only the presence of noradrenergic innervation but also its functional capability [19].

The MIBG scintigraphy method and semiquantitative measurements

Before the examination, it is necessary to establish an appropriate withdrawal period for interfering drugs, taking into account their biological half-lives [5]. For the scintigraphic method of myocardial innervation imaging, ¹²³I-MIBG is intravenously administered at rest, and early (from 10 to 30 min after injection) and delayed (from 3 to 4 h after injection) images are obtained [5,21,26]. Planar images with an anterior view are adequate for the evaluation of cardiac sympathetic function [29]. Tomographic images [single photon emission computed tomography (SPECT)] are often acquired to evaluate the three-dimensional myocardial uptake pattern [1,5,29,30].

Cardiac MIBG uptake in the early phase primarily reflects the integrity and distribution of the presynaptic sympathetic system and the density of the presynaptic cardiac sympathetic nerve endings, whereas the delayed imaging phase also reflects the presynaptic functional tone of the cardiac sympathetic nerve [21,26]. During the hours that follow, MIBG actively enters the sympathetic nerve terminals, mainly in the left ventricular wall, and is quickly washed out in non-neuronal tissue. The delayed phase measurement at 3 to 4 hours after radiotracer injection reflects the active neuronal uptake of MIBG without passive transfer and is recommended for diagnostic studies [21,31,32].

The most common semi-quantitative indices used to interpret the myocardial innervation images are the heart to mediastinum ratio (H/M) and the washout rate obtained from the anterior planar images [28]. Regions of interest (ROIs) are set in the heart (H; target region) and the mediastinum (M; background region) in the early and delayed images to obtain the mean count in each ROI, after which the H/M ratio is calculated [28]. The degree of MIBG accumulation in the heart is evaluated by the H/M ratio. The washout rate is an index that indicates the rate at which MIBG is washed out between the early image and the delayed image by comparing the cardiac counts in the two images [28]. The normal values of these indices have been calculated by performing MIBG scintigraphy in control patients and can differ between various institutions depending on acquisition conditions [1,5,19,28-30]. The normal limit is based on the computation of the 95th percentile of the results in the control group [28].

Most current anti-Parkinson drugs, except MAOB inhibitors, do not affect MIBG uptake [8,10,31,33], but several substances can interfere with MIBG uptake [19,31]. MAO-B inhibitors reduce the H/M ratios of MIBG, and other drugs, such as sympathomimetic agents (e.g., L-threo-DOPS), tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, calcium antagonists, and cardiac glycosides, competitively inhibit MIBG uptake into the sympathetic nerve terminals [19]. Therefore, these drugs should be avoided prior to cardiac sympathetic nervous system assessment, and the results need to be carefully interpreted when patients taking these drugs are analyzed by MIBG scintigraphy (Table 1).

Although cardiac MIBG scintigraphy is a popular diagnostic tool in PD, MIBG scintigraphy has also been evaluated in other organs associated with the sympathetic nervous system, such as the lungs, parotid gland, thyroid, liver and muscle tissues [34-36]. Abnormalities in MIBG uptake are reportedly rare in these organs, although one study [34,36] suggested that thyroid MIBG uptake was reduced in PD [35].

Application of MIBG scintigraphy in various neurological disorders

MIBG scintigraphy was originally developed to assess postganglionic presynaptic cardiac sympathetic nerve endings in a variety of cardiac diseases, including congestive heart failure, ischemic heart disease, coronary artery disease, vasospastic angina pectoris and cardiomyopathy [34,37]. Patients with autonomic failure associated with various neurological diseases of the central and peripheral nervous system showed a reduction of myocardial uptake in MIBG scintigraphy, suggesting cardiac sympathetic dysfunction or denervation [6,34,38-40].

PARKINSON’S DISEASE AND PARKINSON PLUS SYNDROMES

Lewy bodies are intra-cytoplasmic eosinophilic inclusions with a hyaline core and a pale halo that is mainly composed of aggregated α-synuclein [19,41]. The sympathetic nervous system is regularly affected in Lewy body-related disorders [42]. PD is the most common neurodegenerative disorder displaying Lewy body pathology in the brain [43].

Although differential diagnosis of PD from other parkinsonisms is difficult because of the clinical overlap of parkinsonian symptoms [37], the clinical differentiation is very important for deciding upon drug therapy, monitoring patient response to therapy and determining patient prognosis [26].

Parkinson’s disease

Because postganglionic sympathetic failure in PD had been reported [44], MIBG uptake is reportedly decreased in nearly all patients with PD [7-12,45,46], regardless of orthostatic hypotension [10,12,45,46]. The MIBG uptake is reduced even in patients with very early PD as determined using the Hoehn & Yahr (H&Y) staging system, who do not manifest clinically significant signs or symptoms of autonomic dysfunction [8,10,47,48]; reduced MIBG uptake could indicate the eventual disease severity [48,49]. These findings suggest that MIBG scintigraphy could be a useful tool for detecting PD [27,48]. A study showed that the H/M ratios in both the early and delayed images had a tendency to decrease with the progression of the H&Y stages, although this correlation was not statistically significant [48,50].

MIBG scintigraphy also showed a relationship between MIBG uptake and PD phenotype [49]. Generally, MIBG uptake or the H/M ratio is inversely correlated with bradykinesia, rigidity and axial symptoms such as speech, posture and gait [51-53]. However, a study on the predictive value of MIBG scintigraphy regarding the severity and progression of the Parkinsonian motor symptoms suggested that MIBG scintigraphy predicts the velocity of progression on the rigidity and axial symptoms, but not the other motor symptoms of resting tremor, postural tremor and bradykinesia [54].

PD patients could show many non-motor symptoms before the occurrence of motor symptoms. PD cases that initially present these non-motor symptoms are referred to as pre-motor PD, and these cases can also show low MIBG uptake, which suggests that this a good measurement to detect preclinical-stage PD [55]. Olfactory dysfunction, including hyposmia and anosmia, is an important non-motor symptom in PD [56]. Although there have been no large correlation studies between olfactory dysfunction and MIBG scintigraphy, an asymptomatic carrier of an α-synuclein gene mutation showed severe sympathetic myocardial denervation but a normal olfactory test [57]. This report suggests that cardiac sympathetic neuronal degeneration precedes dopaminergic nerve dysfunction [57].

Scans without evidence of dopaminergic defects (SWEDDs) are defined as cases with normal dopamine transporter scans performed in the clinical diagnosis of PD [58,59], and SWEDD cases can be challenging to diagnose and are often misdiagnosed as PD. A recent study also showed that MIBG scintigraphy may help to differentiate patients with SWEDDs from patients with PD [60]. The H/M ratios and washout rate in the MIBG scintigraphy of the SWEDDs group differed from those of both the control and PD groups [60].

Studies of MIBG uptake in genetic PD showed inconsistent results [57,61-64]. Some patients with genetic mutations (in parkin or PARK2, DJ-1, PINK1, and leucine-rich repeat kinase 2) showed normal cardiac MIBG uptake, but others showed lower MIBG uptake [61-64]. Asymptomatic carriers with α-synuclein gene mutations showed low MIBG uptake and tended to develop Lewy body disorders later [57,65].

Differential diagnosis of PD from Parkinson plus syndromes (Table 2)

The sensitivity and specificity of MIBG scintigraphy in differential diagnosis between PD and other parkinsonism disorders ranged from 71 to 100% and from 50 to 100%, respectively, with pooled estimates of 88% [95% confidence interval (CI) 86–90%] and 85% (95% CI 81–88%) [8-10,15,16,27,34,36,48,50,66-75]. In terms of diagnostic performance, many studies have indicated that MIBG scintigraphy is usually a sensitive, but not specific, test for PD [8,15,48,67,68,73].

Autonomic failure is representative of several non-motor deficits that are often encountered in PD [55,68,76-78]. Autonomic failure in PD includes gastrointestinal, sudomotor, thermoregulation, and bladder abnormalities [79-81] and may manifest as urinary frequency/urgency or incontinence, chronic constipation, drooling, erectile failure in men, abnormal sweating, or orthostatic intolerance [81-83]. MSA is a representative neurodegenerative disorder that is characterized by a combination of parkinsonism and autonomic failure [84]. Although autonomic failure is more severe in MSA than in PD 80,85], it also occurs in PD [77,78]. Orthostatic hypotension is a common feature in PD that results from sympathetic post-ganglionic noradrenergic denervation [19,26,44,86-88]. Systematic investigations using MIBG scintigraphy showed a reduced MIBG uptake in PD compared with MSA [7,8,10-12,34,36,46,48,49,71,73-75,89-91]. The pooled sensitivity and specificity for differentiating PD and MSA were 90.2% (95% CI: 84.4%, 93.9%) and 81.9% (95% CI: 56.1%, 94.1%), respectively [8,34,36,48,66,67,73,75,91,92]. For differentiating PD and PSP, the pooled sensitivity and specificity were 91.4% (95% CI: 80.5%, 96.5%) and 78.0% (95% CI: 6.8%, 99.4%), respectively [8,10,34,73,74,92].

A few studies reported reduced MIBG uptake in MSA and PSP, although the reductions were smaller than those in PD [48,93,94]. These findings are supported by the evidence that postganglionic impairment also occurs in patients with MSA [95].

Although there are no data on the pooled analysis for differentiating PD and cortico-basal degeneration (CBD), two studies on CBD showed high sensitivity and low specificity of MIBG scintigraphy [34,67]. A comparative study between PD and CBD showed that the early and delayed H/M ratios in the patients with CBD were significantly higher than those in the patients with PD [96].

Both the early and delayed images for the differential diagnosis between PD and Parkinson plus syndromes showed high specificity of MIBG scintigraphy in cases of PD overall and high sensitivity in the advanced stage of PD [48,50]. However, MIBG scintigraphy in early cases showed low sensitivity in the diagnosis of PD [50], despite the gross reduction of MIBG uptake in the early stage of the disease [31].

There have been several studies about the correlation between the functional images of dopaminergic system and that of cardiac sympathetic system. One study showed a good correlation between MIBG uptake and dopamine uptake [97], but another study found no correlation between the two indices [50,94]. Therefore, one study suggested that MIBG scintigraphy is a useful, complementary tool when it is used with dopaminergic neuroimaging [50].

DLB AND DIFFERENTIAL DIAGNOSIS OF DLB FROM AD (Table 3)

DLB is a typical disorder with Lewy body pathology [18,19], and cardiac uptake of MIBG is also reduced in patients with DLB [8-12,34,90]. Some studies showed that the H/M ratio of DLB was significantly lower than that of PD [48,98]. MIBG scintigraphy is also a good predictor of the future conversion of possible DLB to probable DLB [18].

DLB is clinically characterized by progressive cognitive decline with fluctuations in cognition and alertness, recurrent visual hallucinations, and parkinsonism [99]. The subgroup with the presence of parkinsonism, visual hallucinations and neuroleptic hypersensitivity had a tendency to have low MIBG uptake, in contrast to fluctuations in cognition and alertness [100]. Although the subgroup with the most severe cognitive impairments showed lower MIBG uptake than those with mild and moderate cognitive impairment, this correlation was not found between 2 groups with mild and moderate cognitive deficits [100]. In this study, the subgroup with orthostatic hypotension showed significantly decreased MIBG uptake only when compared to those without orthostatic hypotension [100].

Because DLB shares clinical and pathological features with AD [101], differential diagnosis between DLB and AD is difficult [102]. Several studies have found no correlation of MIBG scintigraphy with the severity or duration of DLB or AD [32,103-105], but many studies have demonstrated reduced MIBG uptake in DLB compared with AD [32,103,104,106-110]. As with the confirmation of the utility of MIBG scintigraphy in discriminating Lewy body-related disorders from non-Lewy body-related disorders [111], the low H/M ratio of MIBG scintigraphy is a possible diagnostic biomarker for DLB and could give a differential diagnostic value in cases where there is doubt about the diagnosis between DLB and AD [17,108]. Compared to occipital hypoperfusion on SPECT, MIBG scintigraphy is powerful tool in detecting DLB [108,112]. Additionally, MIBG scintigraphy has been reported to be more sensitive than cerebrospinal fluid p-tau in terms of differentiating between DLB and AD [109]. In contrast to several studies that reported a normal H/M ratio [32,106], one study found that AD also could show a low H/M ratio, similar to that of PD [48]. This result suggests a relationship between Lewy body pathology and cardiac sympathetic neuronal degeneration in AD [48], whereas the other study found no evidence of significantly low MIBG uptake in AD patients with extrapyramidal sign [104,113].

In terms of diagnostic performance, the pooled sensitivity of MIBG scintigraphy for the detection of DLB was 98%, and the pooled specificity for the differential diagnosis of DLB from other dementias was 94% [99].

However, a lack of pathological data in the discrimination of DLB from AD is also a limitation of MIBG scintigraphy; AD pathology and Lewy body pathology frequently coexist in DLB and AD.

Rapid eye movement sleep behavior disorder

Rapid eye movement sleep behavior disorder (RBD) is found in various neurodegenerative disorders known as synucleinopathies, including PD, DLB and MSA [114], and tauopathies, like AD, PSP and CBD [115]. Patients with synucleinopathies are more likely to have RBD and tend to show RBD in the early stages of the disease compared to those with non-synucleinopathies [114,116-118].

Patients with RBD have Lewy body pathology, which is a common denominator of Lewy body-related disorders such as PD and DLB [119]. Although the prevalence of RBD in the elderly (people of age 70 years or above) was 0.38% [120], PD developed in 38% of those patients within 3.7 years [115,121]. Since the mid-2000s, low MIBG uptake has been reported in patients with RBD [63,111-113]. The low MIBG uptake in RBD patients was similar to those with PD and DLB, or more reduced than in those with early-stage PD [71,122-125]. In addition, a recent study suggests that cardiac denervation precedes nigrostriatal damage in RBD patients [126]. These findings support the hypothesis that RBD is a risk factor for future PD development and could be a marker for predicting PD [121,127,128]. Therefore, RBD patients should be regularly followed up by clinicians because they are good candidates to test the effects of neuroprotective agents before parkinsonian symptoms develop [128].

Pure autonomic failure

Pure autonomic failure (PAF) is a synucleinopathy that is based on Lewy body pathology, similar to PD and DLB, but its clinical presentation is similar to that of MSA [115,129]. PAF shows limited dysfunction of the autonomic system, whereas cerebellar ataxia and parkinsonism with autonomic dysfunction also occur in MSA [130,131]. Low MIBG uptake is also observed in PAF, suggesting cardiac sympathetic denervation in PAF [6,74,132]. Therefore, MIBG scintigraphy can differentiate PAF from MSA.

CONCLUSIONS

In conclusion, MIBG scintigraphy is a useful tool not only for differentiating PD from other neurodegenerative disorders with parkinsonism, but also for assessing disease severity and PD phenotypes. MIBG scintigraphy is also a useful tool in the early diagnosis of patients with pre-motor PD. Low MIBG uptake in patients with DLB, similar to patients with PD, can differentiate DLB from other dementias, including AD. RBD is even a predictor of the progression to neurodegenerative disorders such as PD and DLB, and patients with RBD also show low MIBG uptake.

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

Acknowledgments

We acknowledge the contributions of Yun Joong Kim of the Hallym Institute of Translational Genomics & Bioinformatics, Hallym University Medical Center.

REFERENCES

• 1. Nakajima K, Yoshita M, Matsuo S, Taki J, Kinuya S. Iodine-123-MIBG sympathetic imaging in Lewy-body diseases and related movement disorders. Q J Nucl Med Mol Imaging 2008;52:378–387.PubMed
• 2. Glowniak JV, Turner FE, Gray LL, Palac RT, Lagunas-Solar MC, Woodward WR. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants. J Nucl Med 1989;30:1182–1191.PubMed
• 3. Merlet P, Valette H, Dubois-Randé JL, Moyse D, Duboc D, Dove P, et al. Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med 1992;33:471–477.PubMed
• 4. Hattori N, Schwaiger M. Metaiodobenzylguanidine scintigraphy of the heart: what have we learnt clinically? Eur J Nucl Med 2000;27:1–6.ArticlePubMed
• 5. Yamashina S, Yamazaki J. Neuronal imaging using SPECT. Eur J Nucl Med Mol Imaging 2007;34:939–950.ArticlePubMed
• 6. Hakusui S, Yasuda T, Yanagi T, Tohyama J, Hasegawa Y, Koike Y, et al. A radiological analysis of heart sympathetic functions with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure. J Auton Nerv Syst 1994;49:81–84.ArticlePubMed
• 7. Iwasa K, Nakajima K, Yoshikawa H, Tada A, Taki J, Takamori M. Decreased myocardial 123I-MIBG uptake in Parkinson’s disease. Acta Neurol Scand 1998;97:303–306.ArticlePubMed
• 8. Yoshita M. Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 1998;155:60–67.ArticlePubMed
• 9. Satoh A, Serita T, Seto M, Tomita I, Satoh H, Iwanaga K, et al. Loss of 123I-MIBG uptake by the heart in Parkinson’s disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med 1999;40:371–375.PubMed
• 10. Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H. (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;67:189–194.ArticlePubMedPMC
• 11. Braune S, Reinhardt M, Bathmann J, Krause T, Lehmann M, Lücking CH. Impaired cardiac uptake of meta-[123I] iodobenzylguanidine in Parkinson’s disease with autonomic failure. Acta Neurol Scand 1998;97:307–314.ArticlePubMed
• 12. Braune S, Reinhardt M, Schnitzer R, Riedel A, Lücking CH. Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy. Neurology 1999;53:1020–1025.ArticlePubMed
• 13. Spiegel J, Hellwig D, Farmakis G, Jost WH, Samnick S, Fassbender K, et al. Myocardial sympathetic degeneration correlates with clinical phenotype of Parkinson’s disease. Mov Disord 2007;22:1004–1008.ArticlePubMed
• 14. Lee PH, Kim JS, Shin DH, Yoon SN, Huh K. Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism. J Neurol Neurosurg Psychiatry 2006;77:372–374.ArticlePubMedPMC
• 15. Kim JS, Lee PH, Lee KS, Park JW, Kim YI, Chung YA, et al. Cardiac [123I]metaiodobenzylguanidine scintigraphy for vascular Parkinsonism. Mov Disord 2006;21:1990–1994.ArticlePubMed
• 16. Lee PH, Kim JW, Bang OY, Joo IS, Yoon SN, Huh K. Cardiac 123I-MIBG scintigraphy in patients with essential tremor. Mov Disord 2006;21:1235–1238.ArticlePubMed
• 17. Slaets S, Van Acker F, Versijpt J, Hauth L, Goeman J, Martin JJ, et al. Diagnostic value of MIBG cardiac scintigraphy for differential dementia diagnosis. Int J Geriatr Psychiatry 2014;Nov. 3. [Epub]. http://dx.doi.org/10.1002/gps.4229. ArticlePubMedPMC
• 18. Oda H, Ishii K, Terashima A, Shimada K, Yamane Y, Kawasaki R, et al. Myocardial scintigraphy may predict the conversion to probable dementia with Lewy bodies. Neurology 2013;81:1741–1745.ArticlePubMed
• 19. Rascol O, Schelosky L. 123I-metaiodobenzylguanidine scintigraphy in Parkinson’s disease and related disorders. Mov Disord 2009;24 Suppl 2:S732–S741.Article
• 20. Orimo S, Amino T, Takahashi A, Kojo T, Uchihara T, Mori F, et al. Cardiac sympathetic denervation in Lewy body disease. Parkinsonism Relat Disord 2006;12:S99–S105.Article
• 21. Taki J, Yoshita M, Yamada M, Tonami N. Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: it can be a specific marker for Lewy body disease. Ann Nucl Med 2004;18:453–461.ArticlePubMed
• 22. Jaques S Jr, Tobes MC, Sisson JC, Baker JA, Wieland DM. Comparison of the sodium dependency of uptake of metalodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol 1984;26:539–546.PubMed
• 23. Sisson JC, Shapiro B, Meyers L, Mallette S, Mangner TJ, Wieland DM, et al. Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 1987;28:1625–1636.PubMed
• 24. Sisson JC, Wieland DM, Sherman P, Mangner TJ, Tobes MC, Jacques S Jr. Metaiodobenzylguanidine as an index of the adrenergic nervous system integrity and function. J Nucl Med 1987;28:1620–1624.PubMed
• 25. Sisson JC, Lynch JJ, Johnson J, Jaques S Jr, Wu D, Bolgos G, et al. Scintigraphic detection of regional disruption of adrenergic neurons in the heart. Am Heart J 1988;116(1 Pt 1):67–76.ArticlePubMed
• 26. Lucio CG, Vincenzo C, Antonio R, Oscar T, Antonio R, Luigi M. Neurological applications for myocardial MIBG scintigraphy. Nucl Med Rev Cent East Eur 2013;16:35–41.ArticlePubMed
• 27. Treglia G, Cason E, Stefanelli A, Cocciolillo F, Di Giuda D, Fagioli G, et al. MIBG scintigraphy in differential diagnosis of Parkinsonism: a meta-analysis. Clin Auton Res 2012;22:43–55.ArticlePubMed
• 28. Treglia G, Stefanelli A, Cason E, Cocciolillo F, Di Giuda D, Giordano A. Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson’s disease and multiple-system atrophy: a systematic review and a meta-analysis. Clin Neurol Neurosurg 2011;113:823–829.ArticlePubMed
• 29. Treglia G, Cason E, Gabellini A, Giordano A, Fagioli G. Recent developments in innervation imaging using iodine- 123-metaiodobenzylguanidine scintigraphy in Lewy body diseases. Neurol Sci 2010;31:417–422.ArticlePubMed
• 30. Jost WH, Del Tredici K, Landvogt C, Braune S. Importance of 123I-metaiodobenzylguanidine scintigraphy/single photon emission computed tomography for diagnosis and differential diagnostics of Parkinson syndromes. Neurodegener Dis 2010;7:341–347.ArticlePubMed
• 31. Braune S. The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of parkinsonian syndromes. Clin Auton Res 2001;11:351–355.ArticlePubMed
• 32. Yoshita M, Taki J, Yamada M. A clinical role for [(123)I] MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer’s-type and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2001;71:583–588.ArticlePubMedPMC
• 33. Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO 3rd. Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 2000;133:338–347.ArticlePubMed
• 34. Taki J, Nakajima K, Hwang EH, Matsunari I, Komai K, Yoshita M, et al. Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. taki@med.kanazawa-u. ac.jp. Eur J Nucl Med 2000;27:566–573.ArticlePubMed
• 35. Jang W, Kim JS, Cho JW, Ahn JY, Choi YY, Kim HT. Thyroid MIBG uptake in Parkinson’s disease with diabetes mellitus. Clin Auton Res 2013;23:221–224.ArticlePubMed
• 36. Reinhardt MJ, Jüngling FD, Krause TM, Braune S. Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake. Eur J Nucl Med 2000;27:595–600.ArticlePubMed
• 37. Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I-MIBG myocardial scintigraphy for differentiating Parkinson’s disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord 2012;18:494–500.ArticlePubMed
• 38. Hage FG, Iskandrian AE. Cardiac autonomic denervation in diabetes mellitus. Circ Cardiovasc Imaging 2011;4:79–81.ArticlePubMed
• 39. Scholte AJ, Schuijf JD, Delgado V, Kok JA, Bus MT, Maan AC, et al. Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability. Eur J Nucl Med Mol Imaging 2010;37:1698–1705.ArticlePubMedPMC
• 40. Coutinho MC, Cortez-Dias N, Cantinho G, Conceição I, Oliveira A, Bordalo e Sá A, et al. Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy. Circ Cardiovasc Imaging 2013;6:627–636.ArticlePubMed
• 41. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, et al. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am J Pathol 1998;152:879–884.PubMedPMC
• 42. Wakabayashi K, Takahashi H, Ohama E, Takeda S, Ikuta F. Lewy bodies in the visceral autonomic nervous system in Parkinson’s disease. Adv Neurol 1993;60:609–612.PubMed
• 43. Lindström V, Ihse E, Fagerqvist T, Bergström J, Nordström E, Möller C, et al. Immunotherapy targeting α-synuclein, with relevance for future treatment of Parkinson’s disease and other Lewy body disorders. Immunotherapy 2014;6:141–153.ArticlePubMed
• 44. Senard JM, Valet P, Durrieu G, Berlan M, Tran MA, Montastruc JL, et al. Adrenergic supersensitivity in parkinsonians with orthostatic hypotension. Eur J Clin Invest 1990;20:613–619.ArticlePubMed
• 45. Yoshita M, Hayashi M, Hirai S. Decreased myocardial accumulation of 123I-meta-iodobenzyl guanidine in Parkinson’s disease. Nucl Med Commun 1998;19:137–142.ArticlePubMed
• 46. Takatsu H, Nishida H, Matsuo H, Watanabe S, Nagashima K, Wada H, et al. Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG. J Nucl Med 2000;41:71–77.PubMed
• 47. Oka H, Toyoda C, Yogo M, Mochio S. Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension. Eur J Neurol 2011;18:286–292.ArticlePubMed
• 48. Nagayama H, Hamamoto M, Ueda M, Nagashima J, Katayama Y. Reliability of MIBG myocardial scintigraphy in the diagnosis of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2005;76:249–251.ArticlePubMedPMC
• 49. Saiki S, Hirose G, Sakai K, Kataoka S, Hori A, Saiki M, et al. Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD. J Neurol Sci 2004;220:105–111.ArticlePubMed
• 50. Ishibashi K, Saito Y, Murayama S, Kanemaru K, Oda K, Ishiwata K, et al. Validation of cardiac (123)I-MIBG scintigraphy in patients with Parkinson’s disease who were diagnosed with dopamine PET. Eur J Nucl Med Mol Imaging 2010;37:3–11.ArticlePubMed
• 51. Chung EJ, Kim EG, Kim MS, Bae SK, Seog DH, Oh SJ, et al. Differences in myocardial sympathetic degeneration and the clinical features of the subtypes of Parkinson’s disease. J Clin Neurosci 2011;18:922–925.ArticlePubMed
• 52. Kim JS, Lee KS, Song IU, Kim YI, Kim SH, You IR, et al. Cardiac sympathetic denervation is correlated with Parkinsonian midline motor symptoms. J Neurol Sci 2008;270:122–126.ArticlePubMed
• 53. Suzuki M, Urashima M, Oka H, Hashimoto M, Taira K. Cardiac sympathetic denervation in bradykinesia-dominant Parkinson’s disease. Neuroreport 2007;18:1867–1870.ArticlePubMed
• 54. Dorschner J, Farmakis G, Behnke S, Hellwig D, Schneider S, Fassbender K, et al. Myocardial MIBG scintigraphy may predict the course of motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord 2011;17:372–375.ArticlePubMed
• 55. Sakakibara R, Tateno F, Kishi M, Tsuyusaki Y, Terada H, Inaoka T. MIBG myocardial scintigraphy in pre-motor Parkinson’s disease: a review. Parkinsonism Relat Disord 2014;20:267–273.ArticlePubMed
• 56. Oka H, Toyoda C, Yogo M, Mochio S. Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease. J Neurol 2010;257:969–976.ArticlePubMed
• 57. Tijero B, Gomez-Esteban JC, Llorens V, Lezcano E, Gonzalez-Fernández MC, de Pancorbo MM, et al. Cardiac sympathetic denervation precedes nigrostriatal loss in the E46K mutation of the alpha-synuclein gene (SNCA). Clin Auton Res 2010;20:267–269.ArticlePubMed
• 58. Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol 2003;54:93–101.ArticlePubMed
• 59. Schneider SA, Edwards MJ, Mir P, Cordivari C, Hooker J, Dickson J, et al. Patients with adult-onset dystonic tremor resembling parkinsonian tremor have scans without evidence of dopaminergic deficit (SWEDDs). Mov Disord 2007;22:2210–2215.ArticlePubMed
• 60. Jang W, Kim JS, Cho JW, Kim YH, Kim JY, Choi YY, et al. Cardiac sympathetic denervation in Parkinson’s disease patients with SWEDDs. Neurol Sci 2013;34:1375–1382.ArticlePubMed
• 61. Quattrone A, Bagnato A, Annesi G, Novellino F, Morgante L, Savettieri G, et al. Myocardial 123metaiodobenzylguanidine uptake in genetic Parkinson’s disease. Mov Disord 2008;23:21–27.ArticlePubMed
• 62. Ruiz-Martínez J, Gorostidi A, Goyenechea E, Alzualde A, Poza JJ, Rodríguez F, et al. Olfactory deficits and cardiac 123I-MIBG in Parkinson’s disease related to the LRRK2 R1441G and G2019S mutations. Mov Disord 2011;26:2026–2031.ArticlePubMed
• 63. Orimo S, Amino T, Yokochi M, Kojo T, Uchihara T, Takahashi A, et al. Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in PARK2. Mov Disord 2005;20:1350–1353.ArticlePubMed
• 64. Kim YD, Song IU, Kim JS, Chung SW, Lee KS. Cardiac (123)I-metaiodobenzylguanidine Scintigraphy in a Patient with Familial Parkinsonism with Parkin Gene Mutation. J Mov Disord 2010;3:42–44.ArticlePubMedPMCPDF
• 65. Minguez-Castellanos A, Chamorro CE, Escamilla-Sevilla F, Ortega-Moreno A, Rebollo AC, Gomez-Rio M, et al. Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders?: a cohort study. Neurology 2007;68:2012–2018.ArticlePubMed
• 66. Tateno F, Sakakibara R, Kishi M, Ogawa E, Terada H, Ogata T, et al. Sensitivity and specificity of metaiodobenzylguanidine (MIBG) myocardial accumulation in the diagnosis of Lewy body diseases in a movement disorder clinic. Parkinsonism Relat Disord 2011;17:395–397.ArticlePubMed
• 67. Fröhlich I, Pilloy W, Vaillant M, Diederich NJ. Myocardial MIBG scintigraphy: a useful clinical tool?: a retrospective study in 50 parkinsonian patients. Neurol Sci 2010;31:403–406.ArticlePubMed
• 68. Chung EJ, Lee WY, Yoon WT, Kim BJ, Lee GH. MIBG scintigraphy for differentiating Parkinson’s disease with autonomic dysfunction from Parkinsonism-predominant multiple system atrophy. Mov Disord 2009;24:1650–1655.ArticlePubMed
• 69. Novellino F, Arabia G, Bagnato A, Cascini GL, Salsone M, Nicoletti G, et al. Combined use of DAT-SPECT and cardiac MIBG scintigraphy in mixed tremors. Mov Disord 2009;24:2242–2248.ArticlePubMed
• 70. Sawada H, Oeda T, Yamamoto K, Kitagawa N, Mizuta E, Hosokawa R, et al. Diagnostic accuracy of cardiac metaiodobenzylguanidine scintigraphy in Parkinson disease. Eur J Neurol 2009;16:174–182.ArticlePubMed
• 71. Miyamoto T, Miyamoto M, Suzuki K, Nishibayashi M, Iwanami M, Hirata K. 123I-MIBG cardiac scintigraphy provides clues to the underlying neurodegenerative disorder in idiopathic REM sleep behavior disorder. Sleep 2008;31:717–723.ArticlePubMedPMCPDF
• 72. Nagamachi S, Wakamatsu H, Kiyohara S, Fujita S, Futami S, Tamura S, et al. Usefulness of rCBF analysis in diagnosing Parkinson’s disease: supplemental role with MIBG myocardial scintigraphy. Ann Nucl Med 2008;22:557–564.ArticlePubMed
• 73. Köllensperger M, Seppi K, Liener C, Boesch S, Heute D, Mair KJ, et al. Diffusion weighted imaging best discriminates PD from MSA-P: a comparison with tilt table testing and heart MIBG scintigraphy. Mov Disord 2007;22:1771–1776.ArticlePubMed
• 74. Kashihara K, Ohno M, Kawada S, Okumura Y. Reduced cardiac uptake and enhanced washout of 123I-MIBG in pure autonomic failure occurs conjointly with Parkinson’s disease and dementia with Lewy bodies. J Nucl Med 2006;47:1099–1101.PubMed
• 75. Takatsu H, Nagashima K, Murase M, Fujiwara H, Nishida H, Matsuo H, et al. Differentiating Parkinson disease from multiple-system atrophy by measuring cardiac iodine-123 metaiodobenzylguanidine accumulation. JAMA 2000;284:44–45.ArticlePubMed
• 76. Goldstein DS, Sewell L, Sharabi Y. Autonomic dysfunction in PD: a window to early detection? J Neurol Sci 2011;310:118–122.ArticlePubMed
• 77. Koike Y, Takahashi A. Autonomic dysfunction in Parkinson’s disease. Eur Neurol 1997;38 Suppl 2:8–12.ArticlePubMed
• 78. Senard JM, Raï S, Lapeyre-Mestre M, Brefel C, Rascol O, Rascol A, et al. Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;63:584–589.ArticlePubMedPMC
• 79. Korczyn AD. Autonomic nervous system disturbances in Parkinson’s disease. Adv Neurol 1990;53:463–468.PubMed
• 80. Takahashi A. Autonomic nervous system disorders in Parkinson’s disease. Eur Neurol 1991;31 Suppl 1:41–47.Article
• 81. Sung HY, Park JW, Kim JS. The frequency and severity of gastrointestinal symptoms in patients with early Parkinson’s disease. J Mov Disord 2014;7:7–12.ArticlePubMedPMCPDF
• 82. Kaufmann H, Biaggioni I. Autonomic failure in neurodegenerative disorders. Semin Neurol 2003;23:351–363.ArticlePubMed
• 83. Idiaquez J, Roman GC. Autonomic dysfunction in neurodegenerative dementias. J Neurol Sci 2011;305:22–27.ArticlePubMed
• 84. Wenning GK, Colosimo C, Geser F, Poewe W. Multiple system atrophy. Lancet Neurol 2004;3:93–103.ArticlePubMed
• 85. Magalhães M, Wenning GK, Daniel SE, Quinn NP. Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson’s disease--a retrospective comparison. Acta Neurol Scand 1995;91:98–102.ArticlePubMed
• 86. Goldstein DS, Holmes C, Cannon RO 3rd, Eisenhofer G, Kopin IJ. Sympathetic cardioneuropathy in dysautonomias. N Engl J Med 1997;336:696–702.ArticlePubMed
• 87. Sharabi Y, Li ST, Dendi R, Holmes C, Goldstein DS. Neurotransmitter specificity of sympathetic denervation in Parkinson’s disease. Neurology 2003;60:1036–1039.ArticlePubMed
• 88. Bae HJ, Cheon SM, Kim JW. Orthostatic hypotension in drug-naïve patients with Parkinson’s disease. J Mov Disord 2011;4:33–37.ArticlePubMedPMCPDF
• 89. Yoshita M. Cardiac uptake of [123I]MIBG separates PD from multiple system atrophy. Neurology 2000;54:1877–1878.Article
• 90. Druschky A, Hilz MJ, Platsch G, Radespiel-Tröger M, Druschky K, Kuwert T, et al. Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT. J Neurol Sci 2000;175:3–12.ArticlePubMed
• 91. Courbon F, Brefel-Courbon C, Thalamas C, Alibelli MJ, Berry I, Montastruc JL, et al. Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson’s disease. Mov Disord 2003;18:890–897.ArticlePubMed
• 92. Shin DH, Lee PH, Bang OY, Joo IS, Huh K. Clinical Implications of Cardiac-MIBG SPECT in the Differentiation of Parkinsonian Syndromes. J Clin Neurol 2006;2:51–57.ArticlePubMedPMC
• 93. Hirayama M, Hakusui S, Koike Y, Ito K, Kato T, Ikeda M, et al. A scintigraphical qualitative analysis of peripheral vascular sympathetic function with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure. J Auton Nerv Syst 1995;53:230–234.ArticlePubMed
• 94. Raffel DM, Koeppe RA, Little R, Wang CN, Liu S, Junck L, et al. PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes. J Nucl Med 2006;47:1769–1777.PubMed
• 95. Provitera V, Nolano M, Caporaso G, Stancanelli A, Manganelli F, Iodice R, et al. Postganglionic sudomotor denervation in patients with multiple system atrophy. Neurology 2014;82:2223–2229.ArticlePubMed
• 96. Orimo S, Ozawa E, Nakade S, Hattori H, Tsuchiya K, Taki K, et al. [123I] meta-iodobenzylguanidine myocardial scintigraphy differentiates corticobasal degeneration from Parkinson’s disease. Intern Med 2003;42:127–128.ArticlePubMed
• 97. Spiegel J, Möllers MO, Jost WH, Fuss G, Samnick S, Dillmann U, et al. FP-CIT and MIBG scintigraphy in early Parkinson’s disease. Mov Disord 2005;20:552–561.ArticlePubMed
• 98. Oka H, Yoshioka M, Morita M, Onouchi K, Suzuki M, Ito Y, et al. Reduced cardiac 123I-MIBG uptake reflects cardiac sympathetic dysfunction in Lewy body disease. Neurology 2007;69:1460–1465.ArticlePubMed
• 99. Treglia G, Cason E. Diagnostic performance of myocardial innervation imaging using MIBG scintigraphy in differential diagnosis between dementia with lewy bodies and other dementias: a systematic review and a meta-analysis. J Neuroimaging 2012;22:111–117.ArticlePubMed
• 100. Kobayashi S, Tateno M, Morii H, Utsumi K, Saito T. Decreased cardiac MIBG uptake, its correlation with clinical symptoms in dementia with Lewy bodies. Psychiatry Res 2009;174:76–80.ArticlePubMed
• 101. McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, et al. Dementia with Lewy bodies. Lancet Neurol 2004;3:19–28.ArticlePubMed
• 102. Merdes AR, Hansen LA, Jeste DV, Galasko D, Hofstetter CR, Ho GJ, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology 2003;60:1586–1590.ArticlePubMed
• 103. Oide T, Tokuda T, Momose M, Oguchi K, Nakamura A, Ohara S, et al. Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) myocardial scintigraphy in differentiating between Alzheimer’s disease and dementia with Lewy bodies. Intern Med 2003;42:686–690.ArticlePubMed
• 104. Hanyu H, Shimizu S, Hirao K, Sakurai H, Iwamoto T, Chikamori T, et al. The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis of Lewy body disease in patients with dementia in a memory clinic. Dement Geriatr Cogn Disord 2006;22:379–384.ArticlePubMed
• 105. Suzuki M, Kurita A, Hashimoto M, Fukumitsu N, Abo M, Ito Y, et al. Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson’s disease. J Neurol Sci 2006;240:15–19.ArticlePubMed
• 106. Watanabe H, Ieda T, Katayama T, Takeda A, Aiba I, Doyu M, et al. Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2001;70:781–783.ArticlePubMedPMC
• 107. Jindahra P, Vejjajiva A, Witoonpanich R, Sirisriro R, Sritara C, Pulkes T. Differentiation of dementia with Lewy bodies, Alzheimer’s disease and vascular dementia by cardiac 131I-meta-iodobenzylguanidine (MIBG) uptake (preliminary report). J Med Assoc Thai 2004;87:1176–1181.PubMed
• 108. Hanyu H, Shimizu S, Hirao K, Kanetaka H, Iwamoto T, Chikamori T, et al. Comparative value of brain perfusion SPECT and [(123)I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2006;33:248–253.ArticlePubMed
• 109. Wada-Isoe K, Kitayama M, Nakaso K, Nakashima K. Diagnostic markers for diagnosing dementia with Lewy bodies: CSF and MIBG cardiac scintigraphy study. J Neurol Sci 2007;260:33–37.ArticlePubMed
• 110. Estorch M, Camacho V, Paredes P, Rivera E, RodríguezRevuelto A, Flotats A, et al. Cardiac (123)I-metaiodobenzylguanidine imaging allows early identification of dementia with Lewy bodies during life. Eur J Nucl Med Mol Imaging 2008;35:1636–1641.ArticlePubMed
• 111. King AE, Mintz J, Royall DR. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord 2011;26:1218–1224.ArticlePubMed
• 112. Tateno M, Kobayashi S, Shirasaka T, Furukawa Y, Fujii K, Morii H, et al. Comparison of the usefulness of brain perfusion SPECT and MIBG myocardial scintigraphy for the diagnosis of dementia with Lewy bodies. Dement Geriatr Cogn Disord 2008;26:453–457.ArticlePubMed
• 113. Yoshita M, Taki J, Yokoyama K, Noguchi-Shinohara M, Matsumoto Y, Nakajima K, et al. Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD. Neurology 2006;66:1850–1854.ArticlePubMed
• 114. Boeve BF, Silber MH, Ferman TJ, Lucas JA, Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord 2001;16:622–630.ArticlePubMed
• 115. Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 2006;5:424–432.ArticlePubMed
• 116. Munhoz RP, Teive HA. REM sleep behaviour disorder: how useful is it for the differential diagnosis of parkinsonism? Clin Neurol Neurosurg 2014;127:71–74.ArticlePubMed
• 117. Boeve BF. Mild cognitive impairment associated with underlying Alzheimer’s disease versus Lewy body disease. Parkinsonism Relat Disord 2012;18 Suppl 1:S41–S44.Article
• 118. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain 2000;123(Pt 2):331–339.ArticlePubMedPDF
• 119. Lai YY, Siegel JM. Physiological and anatomical link between Parkinson-like disease and REM sleep behavior disorder. Mol Neurobiol 2003;27:137–152.ArticlePubMedPMC
• 120. Chiu HF, Wing YK, Lam LC, Li SW, Lum CM, Leung T, et al. Sleep-related injury in the elderly--an epidemiological study in Hong Kong. Sleep 2000;23:513–517.ArticlePubMedPDF
• 121. Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 1996;46:388–393.ArticlePubMed
• 122. Miyamoto T, Miyamoto M, Inoue Y, Usui Y, Suzuki K, Hirata K. Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder. Neurology 2006;67:2236–2238.ArticlePubMed
• 123. Kashihara K, Imamura T. Reduced myocardial 123I-MIBG uptake in a patient with idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2007;22:150–151.ArticlePubMed
• 124. Koyama S, Tachibana N, Masaoka Y, Homma I, Kawamura M. Decreased myocardial (123)I-MIBG uptake and impaired facial expression recognition in a patient with REM sleep behavior disorder. Mov Disord 2007;22:746–747.ArticlePubMed
• 125. Kashihara K, Imamura T, Shinya T. Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson’s disease. Parkinsonism Relat Disord 2010;16:252–255.ArticlePubMed
• 126. Salsone M, Labate A, Quattrone A. Cardiac denervation precedes nigrostriatal damage in idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2012;27:1068–1069.ArticlePubMed
• 127. Iranzo A, Molinuevo JL, Santamaría J, Serradell M, Martí MJ, Valldeoriola F, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 2006;5:572–577.ArticlePubMed
• 128. Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 2009;72:1296–1300.ArticlePubMedPMC
• 129. Plazzi G, Cortelli P, Montagna P, De Monte A, Corsini R, Contin M, et al. REM sleep behaviour disorder differentiates pure autonomic failure from multiple system atrophy with autonomic failure. J Neurol Neurosurg Psychiatry 1998;64:683–685.ArticlePubMedPMC
• 130. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology 1996;46:1470.ArticlePubMed
• 131. Wenning GK, Ben Shlomo Y, Magalhães M, Daniel SE, Quinn NP. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994;117(Pt 4):835–845.ArticlePubMedPDF
• 132. Yoshida M, Fukumoto Y, Kuroda Y, Ohkoshi N. Sympathetic denervation of myocardium demonstrated by 123I-MIBG scintigraphy in pure progressive autonomic failure. Eur Neurol 1997;38:291–296.ArticlePubMed
• 133. Hamada K, Hirayama M, Watanabe H, Kobayashi R, Ito H, Ieda T, et al. Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:423–426.ArticlePubMedPMC
• 134. Kikuchi A, Baba T, Hasegawa T, Sugeno N, Konno M, Takeda A. Differentiating Parkinson’s disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test. Parkinsonism Relat Disord 2011;17:698–700.ArticlePubMed
• 135. Südmeyer M, Antke C, Zizek T, Beu M, Nikolaus S, Wojtecki L, et al. Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach. J Nucl Med 2011;52:733–740.ArticlePubMed
• 136. Kurata T, Kametaka S, Ohta Y, Morimoto N, Deguchi S, Deguchi K, et al. PSP as distinguished from CBD, MSA-P and PD by clinical and imaging differences at an early stage. Intern Med 2011;50:2775–2781.ArticlePubMed
• 137. Yoshita M, Arai H, Arai H, Arai T, Asada T, Fujishiro H, et al. Diagnostic Accuracy of 123I-Meta-Iodobenzylguanidine Myocardial Scintigraphy in Dementia with Lewy Bodies: A Multicenter Study. PLoS One 2015;10:e0120540. ArticlePubMedPMC

Figure & Data

References

Citations

Citations to this article as recorded by  

• Conventional magnetic resonance imaging key features for distinguishing pathologically confirmed corticobasal degeneration from its mimics: a retrospective analysis of the J-VAC study
  Keita Sakurai, Aya M. Tokumaru, Mari Yoshida, Yuko Saito, Koichi Wakabayashi, Takashi Komori, Masato Hasegawa, Takeshi Ikeuchi, Yuichi Hayashi, Takayoshi Shimohata, Shigeo Murayama, Yasushi Iwasaki, Toshiki Uchihara, Motoko Sakai, Ichiro Yabe, Satoshi Tan
  Neuroradiology.2024; 66(11): 1917.     CrossRef
• Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder
  Shota Saeda, Yukiyoshi Sumi, Koichi Fujiwara, Hiroshi Kadotani
  BMC Neurology.2024;[Epub]     CrossRef
• Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease
  Don Gueu Park, Woorim Kang, In-Ja Shin, Mauricio Chalita, Hyun-Seok Oh, Dong-Wook Hyun, Hyun Kim, Jongsik Chun, Young-Sil An, Eun Jeong Lee, Jung Han Yoon
  Neurobiology of Disease.2024; 201: 106655.     CrossRef
• Sudden cardiac death in synucleinopathies
  Keivan Javanshiri, Tove Drakenberg, Mattias Haglund, Elisabet Englund
  Journal of Neuropathology & Experimental Neurology.2023; 82(3): 242.     CrossRef
• Optimal Protocol and Clinical Usefulness of 123I-MIBG Cardiac Scintigraphy for Differentiation of Parkinson’s Disease and Dementia with Lewy Body from Non-Parkinson’s Diseases
  In Kook Chun
  Nuclear Medicine and Molecular Imaging.2023; 57(3): 145.     CrossRef
• Cardiac 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy in Parkinson’s Disease: A Comprehensive Review
  Jamir Pitton Rissardo, Ana Letícia Fornari Caprara
  Brain Sciences.2023; 13(10): 1471.     CrossRef
• Differentiating Dementia with Lewy Bodies from Alzheimer's Disease Using the Fall Risk Evaluation Questionnaire
  Masashi Tsujimoto, Keisuke Suzuki, Akinori Takeda, Naoki Saji, Takashi Sakurai, Yukihiko Washimi
  Internal Medicine.2022; 61(11): 1687.     CrossRef
• Association of plasma α-synuclein with cardiac 123I-MIBG scintigraphy in early Parkinson’s disease
  Don Gueu Park, Juhee Kang, Young-Sil An, Jaerak Chang, Jung Han Yoon
  Neuroscience Letters.2022; 770: 136399.     CrossRef
• Clinical and imaging evidence of brain-first and body-first Parkinson's disease
  Jacob Horsager, Karoline Knudsen, Michael Sommerauer
  Neurobiology of Disease.2022; 164: 105626.     CrossRef
• Cardiac Alpha-Synuclein Is Present in Alpha-Synucleinopathies
  Keivan Javanshiri, Tove Drakenberg, Mattias Haglund, Elisabet Englund
  Journal of Parkinson's Disease.2022; 12(4): 1125.     CrossRef
• Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age
  G. Roberts, J.J. Lloyd, J.P.M. Kane, R. Durcan, S. Lawley, K. Howe, G.S. Petrides, J.T. O’Brien, A.J. Thomas
  Journal of Nuclear Cardiology.2021; 28(4): 1692.     CrossRef
• Uniformity of cardiac 123I-MIBG uptake on SPECT images in older adults with normal cognition and patients with dementia
  Gemma Roberts, Jim J. Lloyd, Elizabeth Jefferson, Joseph P.M. Kane, Rory Durcan, Sarah Lawley, George S. Petrides, Kim Howe, Iftikhar Haq, John T. O’Brien, Alan J. Thomas
  Journal of Nuclear Cardiology.2021; 28(5): 2151.     CrossRef
• Myocardial Sympathetic Innervation Imaging with MIBG in Dementia with Lewy Bodies
  Gagandeep Choudhary, Pradeep Bhambhvani
  Journal of Nuclear Cardiology.2021; 28(5): 2164.     CrossRef
• Identification of BAG2 and Cathepsin D as Plasma Biomarkers for Parkinson’s Disease
  Juhee Kang, Jae Whan Kim, Hansol Heo, Jihyun Lee, Kwan Yong Park, Jung Han Yoon, Jaerak Chang
  Clinical and Translational Science.2021; 14(2): 606.     CrossRef
• Gastrointestinal Dysfunction in Parkinson’s Disease
  Casper Skjærbæk, Karoline Knudsen, Jacob Horsager, Per Borghammer
  Journal of Clinical Medicine.2021; 10(3): 493.     CrossRef
• Management of Hypertension and Blood Pressure Dysregulation in Patients with Parkinson’s Disease—a Systematic Review
  Vasiliki Katsi, Ilias Papakonstantinou, Eirini Solomou, Alexios S. Antonopoulos, Charalambos Vlachopoulos, Konstantinos Tsioufis
  Current Hypertension Reports.2021;[Epub]     CrossRef
• Lewy Body Dementias: A Coin with Two Sides?
  Ángela Milán-Tomás, Marta Fernández-Matarrubia, María Cruz Rodríguez-Oroz
  Behavioral Sciences.2021; 11(7): 94.     CrossRef
• Cardiac Autonomic Dysfunction Is Associated with Severity of REM Sleep without Atonia in Isolated REM Sleep Behavior Disorder
  Sooyeoun You, Kyoung Sook Won, Keun Tae Kim, Hyang Woon Lee, Yong Won Cho
  Journal of Clinical Medicine.2021; 10(22): 5414.     CrossRef
• A diagnostic strategy for Lewy body disease using DAT-SPECT, MIBG and Combined index
  Fumi Sakamoto, Shinya Shiraishi, Koji Ogasawara, Noriko Tsuda, Masataka Nakagawa, Seiji Tomiguchi, Yasuyuki Yamashita
  Annals of Nuclear Medicine.2020; 34(6): 415.     CrossRef
• Difference in cardiovascular response during orthostatic stress in Parkinson’s disease and multiple system atrophy
  Tomohiko Nakamura, Masashi Suzuki, Masamichi Ueda, Yumiko Harada, Masaaki Hirayama, Masahisa Katsuno
  Journal of Neural Transmission.2020; 127(10): 1377.     CrossRef
• Striatal dopamine activity and myocardial 123I-metaiodobenzylguanidine uptake in early Parkinson's disease
  Yoon-Sang Oh, Joong-Seok Kim, Sang-Won Yoo, Eo-Jin Hwang, Chul Hyoung Lyoo, Kwang-Soo Lee
  Parkinsonism & Related Disorders.2019; 63: 156.     CrossRef
• Initial Versus Follow-up Sequential Myocardial 123I-MIBG Scintigraphy to Discriminate Parkinson Disease From Atypical Parkinsonian Syndromes
  Dong-Woo Ryu, Joong-Seok Kim, Jee-Eun Lee, Yoon-Sang Oh, Sang-Won Yoo, Ie Ryung Yoo, Kwang-Soo Lee
  Clinical Nuclear Medicine.2019; 44(4): 282.     CrossRef
• Cardiac 123I-MIBG planar heart to mediastinum ratios depend on patient size; phantom studies suggest SPECT-CT could improve quantification
  Gemma Roberts, Jim J Lloyd, George S Petrides, John T O’Brien, Alan J Thomas
  Biomedical Physics & Engineering Express.2019; 6(1): 015011.     CrossRef
• Does sympathetic dysfunction occur before denervation in pure autonomic failure?
  Ling Guo, Murray D. Esler, Carolina Sari, Sarah Phillips, Elisabeth A. Lambert, Nora E. Straznicky, Gavin W. Lambert, Susan J. Corcoran
  Clinical Science.2018; 132(1): 1.     CrossRef
• Validation of Iodine-131-meta-iodobenzylguanidine cardiac scintigraphy in Parkinsonism: A preliminary study
  Dan Xu, Wenjia Zhu, Li Huo, Shikun Zhu, Fang Li, Han Wang
  Parkinsonism & Related Disorders.2018;[Epub]     CrossRef
• Extensive Delayed Brain Atrophy after Resuscitation in a Patient with Multiple System Atrophy
  Sazuku Nisitani, Hirofumi Miyoshi, Yoji Katsuoka
  Frontiers in Neurology.2018;[Epub]     CrossRef
• Optimizing Parkinson’s disease diagnosis: the role of a dual nuclear imaging algorithm
  J. William Langston, Jesse C. Wiley, Michele Tagliati
  npj Parkinson's Disease.2018;[Epub]     CrossRef
• Diagnostic biomarkers for Parkinson’s disease at a glance: where are we?
  Ilaria Cova, Alberto Priori
  Journal of Neural Transmission.2018; 125(10): 1417.     CrossRef
• Imaging the Autonomic Nervous System in Parkinson’s Disease
  Karoline Knudsen, Per Borghammer
  Current Neurology and Neuroscience Reports.2018;[Epub]     CrossRef
• A Review of Dementia with Lewy Bodies' Impact, Diagnostic Criteria and Treatment
  Samuel D. Capouch, Martin R. Farlow, Jared R. Brosch
  Neurology and Therapy.2018; 7(2): 249.     CrossRef
• The Utility of the Combined Use of ¹²³I-FP-CIT and ¹²³I-MIBG Myocardial Scintigraphy in Differentiating Parkinson’s Disease from Other Parkinsonian Syndromes
  Eiji Matsusue, Yoshio Fujihara, Kenichiro Tanaka, Yuki Aozasa, Manabu Shimoda, Hiroyuki Nakayasu, Kazuhiko Nakamura, Toshihide Ogawa
  Yonago Acta Medica.2018; 61(2): 117.     CrossRef
• Correction of collimator-dependent differences in the heart-to-mediastinum ratio in 123I-metaiodobenzylguanidine cardiac sympathetic imaging: Determination of conversion equations using point-source imaging
  Yusuke Inoue, Yutaka Abe, Kei Kikuchi, Keiji Matsunaga, Ray Masuda, Kazutoshi Nishiyama
  Journal of Nuclear Cardiology.2017; 24(5): 1725.     CrossRef
• Normal ‘heart’ in Parkinson's disease: is this a distinct clinical phenotype?
  J.‐S. Kim, H.‐E. Park, I.‐S. Park, Y.‐S. Oh, D.‐W. Ryu, I.‐U. Song, Y.‐A. Jung, I. R. Yoo, H.‐S. Choi, P. H. Lee, K.‐S. Lee
  European Journal of Neurology.2017; 24(2): 349.     CrossRef
• Diagnosis of dementia with Lewy bodies: can 123I-IMP and 123I-MIBG scintigraphy yield new core features?
  Fumi Sakamoto, Shinya Shiraishi, Noriko Tsuda, Mamoru Hashimoto, Seiji Tomiguchi, Manabu Ikeda, Yasuyuki Yamashita
  The British Journal of Radiology.2017;[Epub]     CrossRef
• Imaging Parkinson’s disease below the neck
  Per Borghammer, Karoline Knudsen, Tatyana D. Fedorova, David J. Brooks
  npj Parkinson's Disease.2017;[Epub]     CrossRef
• The utility of the combination of a SPECT study with [123I]-FP-CIT of dopamine transporters and [123I]-MIBG myocardial scintigraphy in differentiating Parkinson disease from other degenerative parkinsonian syndromes
  Naoto Uyama, Hideki Otsuka, Takayoshi Shinya, Yoichi Otomi, Masafumi Harada, Wataru Sako, Yuishin Izumi, Ryuji Kaji, Yuya Watanabe, Satoru Takashi, Yamato Kunikane
  Nuclear Medicine Communications.2017; 38(6): 487.     CrossRef
• Cardiac sympathetic denervation and dementia in de novo Parkinson's disease: A 7-year follow-up study
  Mun Hee Choi, Jung Han Yoon, Suk Woo Yong
  Journal of the Neurological Sciences.2017; 381: 291.     CrossRef
• Cardiovascular autonomic dysfunctions in elderly patients with essential tremor: comparison with healthy controls
  Joong-Seok Kim, Yoon-Sang Oh, Hyung-Eun Park, Si-Hoon Lee, Jeong-Wook Park, In-Uk Song, Jae-Young An, Hun-Jun Park, Byung-Chul Son, Kwang-Soo Lee
  Neurological Sciences.2016; 37(5): 711.     CrossRef
• Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder
  Joong-Seok Kim, Hyung-Eun Park, Yoon-Sang Oh, Si-Hoon Lee, Jeong-Wook Park, Byung-chul Son, Kwang-Soo Lee
  Journal of the Neurological Sciences.2016; 362: 59.     CrossRef
• [123]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies
  J. J. van der Zande, J. Booij, P. Scheltens, P. G. H. M. Raijmakers, A. W. Lemstra
  European Journal of Nuclear Medicine and Molecular Imaging.2016; 43(6): 1060.     CrossRef
• Is dopamine transporter invariably impaired at the time of diagnosis in dementia with Lewy bodies?
  Flavio Nobili, Dario Arnaldi, Silvia Morbelli
  European Journal of Nuclear Medicine and Molecular Imaging.2016; 43(6): 1056.     CrossRef
• Imaging Systemic Dysfunction in Parkinson’s Disease
  Per Borghammer, Karoline Knudsen, David J. Brooks
  Current Neurology and Neuroscience Reports.2016;[Epub]     CrossRef
• 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane single photon emission computed tomography and 123I‐metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study
  Pietro Tiraboschi, Angelo Corso, Ugo Paolo Guerra, Flavio Nobili, Arnoldo Piccardo, Maria Lucia Calcagni, Duccio Volterrani, Diego Cecchin, Mauro Tettamanti, Luigi Antelmi, Simone Vidale, Leonardo Sacco, Maria Merello, Stefano Stefanini, Anna Micheli, Pao
  Annals of Neurology.2016; 80(3): 368.     CrossRef
• On the Utility of MIBG SPECT/CT in Evaluating Cardiac Sympathetic Dysfunction in Lewy Body Diseases
  Hayato Odagiri, Toru Baba, Yoshiyuki Nishio, Osamu Iizuka, Minoru Matsuda, Kentaro Inoue, Akio Kikuchi, Takafumi Hasegawa, Masashi Aoki, Atsushi Takeda, Yasuyuki Taki, Etsuro Mori, John Duda
  PLOS ONE.2016; 11(4): e0152746.     CrossRef
• 123I-MIBG myocardial scintigraphy and neurocirculatory abnormalities in patients with dementia with Lewy bodies and Alzheimer's disease
  Joong-Seok Kim, Hyung-Eun Park, Yoon-Sang Oh, In-Uk Song, Dong-Won Yang, Jeong-Wook Park, Kwang-Soo Lee
  Journal of the Neurological Sciences.2015; 357(1-2): 173.     CrossRef
• Orthostatic hypotension: managing a difficult problem
  Pearl K Jones, Brett H Shaw, Satish R Raj
  Expert Review of Cardiovascular Therapy.2015; 13(11): 1263.     CrossRef

Comments on this article