Relationship between 123I-MIBG scintigrams and REM sleep behavior disorder in Parkinson’s disease

doi:10.1016/j.parkreldis.2010.08.011

Parkinsonism & Related Disorders

Volume 16, Issue 10, December 2010, Pages 683-685

https://doi.org/10.1016/j.parkreldis.2010.08.011 Get rights and content

Abstract

Background

Uptake of ¹²³I-labeled meta-iodobenzylguanidine (MIBG) in myocardial scintigrams has been shown to be as low in patients with idiopathic RBD as in Parkinson’s disease (PD) patients.

Aim for study

To clarify whether the existence of RBD accelerates autonomic dysfunction in PD, we investigated the association between MIBG scintigraphic findings and RBD measures among non-dementia PD patients.

Subjects & methods

We conducted clinical interviews to assess REM sleep behavior disorder (RBD) symptoms, and performed polysomnograms (PSG) recordings and MIBG scintigrams on 49 PD patients. The patients were divided into three groups (PD with clinical RBD, PD with subclinical RBD, and PD with normal REM sleep).

Results

PD patients with clinical RBD had reduced MIBG uptake as determined by heart-to-mediastinum ratios of the delayed image compared to those with subclinical RBD and those with normal REM sleep. Multiple linear regression analysis revealed that only the existence of RBD symptoms was significantly associated with reduced MIBG uptake among PD patients without dementia after adjusting for demographic and PD symptom-related variables.

Conclusion

PD patients with clinical RBD might suffer from a wider α-synuclein pathology, including reduced cardiac sympathetic ganglia function as reflected by a lowered MIBG uptake.

Introduction

REM sleep behavior disorder (RBD) is characterized by vigorous and injurious behaviors related to vivid, action-filled, and violent dreams in nocturnal REM sleep. RBD is diagnosed when a patient has both violent dream enactment behavior and REM sleep without atonia (RWA) on polysomnograms (PSG). RBD has been widely accepted as one of the important co-morbidities of PD [1] and has been proposed to be one of the risk factors for developing hallucinations [2] [3] in PD patients. Moreover, orthostatic abnormalities were found to be more frequent in PD patients having RBD compared to those without these symptoms [3].

Cardiac uptake of ¹²³I-labeled meta-iodobenzylguanidine (MIBG) on scintigrams is known to be reduced in PD patients [4]. Notably, reduced MIBG uptake on scintigrams in patients with idiopathic RBD is quite similar to that of PD patients [5]. However, it has not been determined whether reductions in MIBG uptake are lower in PD patients with RBD versus those without RBD. To clarify this issue, we investigated the association between MIBG scintigraphic findings and RBD measures among PD patients.

Section snippets

Methods

This study was approved by the ethics committees of Tottori University, and all patients gave informed consent to take part in it. Patients with PD who had been hospitalized in the Department of Neurology at the University Hospital from July 2004 to June 2008 were targeted for this study, and forty-nine PD patients agreed to participate. The mean follow-up period on the subject patients was 6.3 ± 5.1 years. They had been receiving oral dopaminergic agents [levodopa dose equivalents (LDEs) [6]

Results

Twenty-six of the 49 PD patients without dementia had RWA on PSG (53.1%); 18 patients were classified as having clinical RBD (36.7%), including 8 with violent behavior and 10 with non-violent behavior. Eight patients were classified as displaying subclinical RBD (16.3%). The other 23 patients had normal REM sleep (46.9%). There were no significant differences in any of the above descriptive parameters among the three PD groups (Table 1).

There was a significant difference in H/M ratios on the

Discussion

Our results confirmed that MIBG uptake is decreased in non-dementia PD patients with clinical RBD. Moreover, among the studied variables, the existence of RBD symptoms alone was associated with reduced MIBG uptake among PD patients. Interestingly, our results indicate that patients with subclinical RBD do not show significantly reduced MIBG uptake. This finding raises the possibility that neuronal loss and inclusion of Lewy bodies in the sympathetic ganglia as reflected by the reduced MIBG

Acknowledgements

We would like thank Mr. Tatsuo Kagimura of Tokyo Medical University for his generous help with the statistical analysis.

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Cardiac uptake of [¹²³I]MIBG separates Parkinson’s disease from multiple system atrophy
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Cited by (57)

Olfactory function deteriorates in patients with Parkinson's disease complicated with REM sleep behavior disorder
2020, eNeurologicalSci
It is not concluded whether the association between olfactory dysfunction and REM sleep behavior disorder (RBD) were worsen cognitive function in patients with Parkinson's disease (PD). We sought to evaluate the impact of these symptoms in PD.
We examined 62 patients with PD using an olfactory test (Odor Stick Identification Test for Japanese: OSIT-J) and polysomnography (PSG). We divided the patients into 3 groups: PD with clinical RBD (n = 32), PD with subclinical RBD (n = 11), and PD with normal REM sleep (n = 19). We compared their clinical backgrounds, results of OSIT-J, autonomic functions, and cognitive functions such as Montreal cognitive assessment Japanese version (MoCA-J). Some factors associated with RBD were analyzed by multiple regression.
There were significant differences in the results of OSIT-J, and autonomic and cognitive functions between the 3 groups. There were significant differences in the total OSIT-J score between the 3 groups (PD with clinical RBD: 3.3 ± 2.2, PD with subclinical RBD: 4.0 ± 2.6, PD with normal REM sleep: 6.7 ± 3.0, p < 0.001). Patients in the group with PD with clinical RBD had a significantly lower score than those with normal REM sleep (p < 0.001). Logistic regression analysis showed that OSIT-J score was significantly associated with RBD. The PD group with clinical RBD had more patients with mild cognitive impairment than the group with normal REM sleep. Multiple regression analysis revealed that olfactory dysfunction was correlated with MoCA-J.
Olfactory dysfunction is associated with RBD. Especially, it is important to screen olfactory function in RBD complicated patients with PD in view of cognitive impairment.
Sensitivity and specificity of cardiac <sup>123</sup>I-MIBG scintigraphy for diagnosis of early-phase Parkinson's disease
2019, Journal of the Neurological Sciences
Citation Excerpt :
Motor symptoms at the time of the MIBG test were evaluated based on medical history and standardized neurological examinations carried out by several neurologists (MK, TM, SF, JT, YT). Non-motor symptoms at the time of the MIBG test were also defined based on medical history and/or physical findings, and were classified as follows: (1) dementia and mild cognitive impairments: symptoms of memory problems that yielded an apparent disturbance of daily life, and/or Mini-Mental State Examination (MMSE) scores of <20 points [16]; (2) orthostatic hypotension: subjectively, with complaints of lightheadedness or blurred vision in the upright posture and/or a decrease in systolic blood pressure of at least 20 mmHg during the head-up tilt test [17]; (3) depression: depressive symptoms and/or current/past use of anti-depressants; (4) constipation: bowel movement of twice a week or less and/or a chronic use of laxatives; (5) urinary disturbance: frequent urination, nocturia, and/or chronic use of drugs for the treatment of these symptoms; (6) hallucination and delusion: apparent episodes of vivid and visual hallucinations and/or a delusional disorder pointed out by others; (7) REM sleep behavior disorder (RBD): symptoms of arm/leg movement, and/or shouting, speaking, or laughing loudly during sleep that was reported by a bed-partner of a patient [18]; and (8) other: non-motor symptoms that did not fit into categories (1)–(7). We defined PD severity according to the H & Y stage at the time of the MIBG test [19].
The purpose of this study was to investigate the diagnostic accuracy of cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy for the diagnosis of Parkinson's disease (PD), especially in the early stages.
We investigated 600 patients who underwent cardiac ¹²³I-MIBG scintigraphy to diagnose their parkinsonism and/or cognitive impairment. Of 600 research subjects, 272 patients were clinically diagnosed with PD. MIBG uptake was compared between patients with PD and other diseases. Furthermore, the sensitivity and specificity of cardiac ¹²³I-MIBG scintigraphy to diagnose PD was estimated by disease duration (<3 years: early group vs. over 3 years: late group). We also assessed the relationship between MIBG uptake and Hoehn & Yahr stage.
MIBG uptakes of PD patients were significantly decreased compared with those of other diseases except dementia with Lewy bodies and pure autonomic failure (p < .05 for all). In the early group, the sensitivity and specificity of the delayed heart to mediastinum (H/M) ratio were 68.7% and 91.7%, respectively, while in the late group, the sensitivity was 86.3% and the specificity was 74.0%. In addition, the early and delayed H/M ratios were decreased with higher Hoehn & Yahr stages in PD patients.
Our findings demonstrated that cardiac ¹²³I-MIBG scintigraphy had sufficient diagnostic accuracy to detect the early phase of PD. Indeed, this study of a large number of patients provides further external validation that MIBG has diagnostic ability to distinguish PD from atypical parkinsonism.
Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder
2019, Autonomic Neuroscience: Basic and Clinical
Citation Excerpt :
In PD, on the other hand, the H/M ratio decreased with disease duration. Other studies have demonstrated a more marked reduction of MIBG cardiac uptake in iRBD compared to early PD (Kashihara et al., 2010), and also in PD with RBD compared to PD without RBD (Nomura et al., 2010; Miyamoto et al., 2011), again suggesting that cardiac post-ganglionic sympathetic denervation may be more closely associated with the presence of RBD than with PD. More recently, in 2016, Kim et al. (Kim et al., 2016) demonstrated that RBD was closely associated with orthostatic hypotension (OH) and cardiac sympathetic denervation in patients with early and mild PD.
Autonomic dysfunction is common in REM-sleep behavior disorder (RBD). Several studies have demonstrated abnormalities in heart rate variability, cardiac scintigraphy, and cardiovascular autonomic reflex testing. In addition, the type and severity of these abnormalities may correlate with rate of phenoconversion from idiopathic RBD (iRBD) to manifest neurodegenerative disease. This article summarizes the current literature on autonomic impairment in iRBD, with specific focus on the role of autonomic impairment as a potential biomarker of disease progression. REM sleep physiology and relevant anatomy is also discussed in relation to the central autonomic network and autonomic neurodegeneration.
Restless legs syndrome, leg motor restlessness and their variants in patients with Parkinson's disease and related disorders
2018, Journal of the Neurological Sciences
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However, the reason for the difference in the rate of unilateral/bilateral RLS/LMR between our study and the study by Zhu et al. [34] is unclear, but may be due to differences in the study population. In a previous study, PD patients with RBD showed reduced MIBG uptake compared with PD patients without RBD [37]. However, the difference in cardiac MIBG uptake between PD with and without restlessness has not been assessed previously.
The objective of this study was to investigate the prevalence of restless leg syndrome (RLS), leg motor restlessness (LMR) and RLS/LMR variants and their relationship with clinical factors in patients with Parkinson's disease (PD) and related disorders.
Sixty-three PD patients, 17 multiple system atrophy (MSA) patients and 11 progressive supranuclear palsy (PSP) patients were included in this study. Through face-to-face interviews, the patients were diagnosed with RLS/LMR, or with RLS/LMR variants in which the symptoms occur predominantly in body parts other than the legs.
The frequency of RLS, LMR, RLS variants and LMR variants was as follows: PD (12.7%, 11.1%, 0% and 1.6%); MSA (5.9%, 11.8%, 0% and 0%); and PSP (0%, 9.1%, 0% and 0%). Restlessness without the urge to move was observed in 25.4% of the PD patients, 11.8% of the MSA patients and 0% of the PSP patients. The PD patients with restlessness exhibited higher Hoehn and Yahr stages and higher scores on the Scales for Outcomes in PD-Autonomic, PD sleep scale-2 and Beck Depression Inventory-II. The olfactory functioning, 123I-MIBG myocardial scintigraphy uptake and dopamine transporter single photon emission computed tomography findings did not differ between the PD patients with restlessness and those without. The severity of RLS was correlated with the autonomic symptoms among the PD patients with restlessness.
PD with restlessness was characterized by increased autonomic, sleep and depressive symptoms. Further studies including a large sample are warranted to characterize restlessness in PD and related disorders.
In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study
2018, The Lancet Neurology
Accumulating evidence suggests that α-synuclein aggregates—a defining pathology of Parkinson's disease—display cell-to-cell transmission. α-synuclein aggregation is hypothesised to start in autonomic nerve terminals years before the appearance of motor symptoms, and subsequently spread via autonomic nerves to the spinal cord and brainstem. To assess this hypothesis, we investigated sympathetic, parasympathetic, noradrenergic, and dopaminergic innervation in patients with idiopathic rapid eye movement (REM) sleep behaviour disorder, a prodromal phenotype of Parkinson's disease.
In this prospective, case-control study, we recruited patients with idiopathic REM sleep behaviour disorder, confirmed by polysomnography, without clinical signs of parkinsonism or dementia, via advertisement and through sleep clinics in Denmark. We used ¹¹C-donepezil PET and CT to assess cholinergic (parasympathetic) gut innervation, ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure integrity of pigmented neurons of the locus coeruleus, ¹¹C-methylreboxetine (MeNER) PET to assess noradrenergic nerve terminals originating in the locus coeruleus, and ¹⁸F-dihydroxyphenylalanine (DOPA) PET to assess nigrostriatal dopamine storage capacity. For each imaging modality, we compared patients with idiopathic REM sleep behaviour disorder with previously published reference data of controls without neurological disorders or cognitive impairment and with symptomatic patients with Parkinson's disease. We assessed imaging data using one-way ANOVA corrected for multiple comparisons.
Between June 3, 2016, and Dec 19, 2017, we recruited 22 consecutive patients with idiopathic REM sleep behaviour disorder to the study. Compared with controls, patients with idiopathic REM sleep behaviour disorder had decreased colonic ¹¹C-donepezil uptake (−0·322, 95% CI −0·112 to −0·531; p=0·0020), ¹²³I-MIBG heart:mediastinum ratio (−0·508, −0·353 to −0·664; p<0·0001), neuromelanin-sensitive MRI locus coeruleus:pons ratio (−0·059, −0·019 to −0·099; p=0·0028), and putaminal ¹⁸F-DOPA uptake (Ki; −0·0023, −0·0009 to −0·0037; p=0·0013). No between-group differences were detected between idiopathic REM sleep behaviour disorder and Parkinson's disease groups with respect to ¹¹C-donepezil (p=0·39), ¹²³I-MIBG (p>0·99), neuromelanin-sensitive MRI (p=0·96), and ¹¹C-MeNER (p=0·56). By contrast, 15 (71%) of 21 patients with idiopathic REM sleep behaviour disorder had ¹⁸F-DOPA Ki values within normal limits, whereas all patients with Parkinson's disease had significantly decreased ¹⁸F-DOPA Ki values when compared with patients with idiopathic REM sleep behaviour disorder (p<0·0001).
Patients with idiopathic REM sleep behaviour disorder had fully developed pathology in the peripheral autonomic nervous system and the locus coeruleus, equal to that in diagnosed Parkinson's disease. These patients also showed noradrenergic thalamic denervation, but most had normal putaminal dopaminergic storage capacity. This caudorostral gradient of dysfunction supports the hypothesis that α-synuclein pathology in Parkinson's disease initially targets peripheral autonomic nerves and then spreads rostrally to the brainstem.
Lundbeck Foundation, Jascha Foundation, and the Swiss National Foundation.
Differences in clinical characteristics when REM sleep behavior disorder precedes or comes after the onset of Parkinson's disease
2017, Journal of the Neurological Sciences
Citation Excerpt :
Approximately one third of patients with PD have clinical symptoms of RBD [2]. Moreover, RBD may be a risk factor for deterioration of motor, autonomic, and cognitive functions in patients with PD [3]. Two studies have suggested that patients with PD and clinical symptoms of RBD developed dementia over a shorter period than those with normal REM sleep [4].
Rapid eye movement (REM) sleep behavior disorder (RBD) is important not only as a preclinical symptom of Parkinson's disease (PD), but also as an aggravating symptom of PD. However, it is not known whether the onset of RBD in relation to PD affects the clinical characteristics of PD. A cross-sectional study comparing clinical characteristics of PD between patients with RBD occurring before and after the onset of PD was conducted.
Interviews regarding RBD symptoms were conducted and polysomnography was performed on 136 patients with PD. Patients with PD were divided into a group with RBD and a group without RBD. Moreover, the group with RBD was subdivided into those with RBD before the onset of PD (RBD → PD) and those with RBD after the onset of PD (PD → RBD). Clinical characteristics of the patients with and without RBD, and PD with RBD → PD and PD → RBD were compared.
Patients with RBD (47 PD patients) had more severe parkinsonian symptoms, autonomic dysfunction, and cognitive impairment than those without RBD (89 PD patients). Moreover, 38 PD patients with PD → RBD had greater cognitive impairment including Mini-metal examination than 9 with RBD → PD in spite of similar motor and autonomic dysfunction with similar dopaminergic agents.
The occurrence of RBD after the onset of PD might be an important factor aggravating cognitive function.

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^☆: The review of this paper was entirely handled by an Associate Editor, Eng-King Tan.

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Short communicationRelationship between 123I-MIBG scintigrams and REM sleep behavior disorder in Parkinson’s disease☆

Abstract

Background

Aim for study

Subjects & methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgements

J Neurol Sci

J Neurol Sci

International classification of sleep disorders: diagnostic and coding manual

Visual hallucinations as REM sleep behavior disorders in patients with Parkinson’s disease

Mov Disord

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder

Mov Disord

Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy

Neurology

Short communication
Relationship between ¹²³I-MIBG scintigrams and REM sleep behavior disorder in Parkinson’s disease☆

Cardiac uptake of [¹²³I]MIBG separates Parkinson’s disease from multiple system atrophy