Elsevier

Sleep Medicine

Volume 13, Issue 1, January 2012, Pages 102-106
Sleep Medicine

Brief Communication
Preclinical substantia nigra dysfunction in rapid eye movement sleep behaviour disorder

https://doi.org/10.1016/j.sleep.2011.03.024Get rights and content

Abstract

Objectives

Transcranial sonography (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in people with Parkinson’s disease and in approximately 10% of healthy subjects. It is hypothesized that SN hyperechogenicity in healthy subjects and patients with idiopathic rapid eye movement (REM) sleep behaviour disorder (iRBD) patients is a marker of vulnerability for Parkinson’s disease.

Methods

TCS and positron emission tomography (PET) with 6-[18F] fluoro-meta-tyrosine (FMT), which can assess the level of the presynaptic dopaminergic nerve, were performed in 19 male patients with iRBD, mean age 66.4 (standard deviation [SD] 4.9) years, to assess nigrostriatal function.

Results

Nine patients had pathological SN hyperechogenicity (mean age 66.8 [SD 3.9] years; 0.31 [SD 0.12] cm2) and 10 patients did not have SN hyperechogenicity (mean age 66.0 [SD 5.8] years; 0.11 [SD 0.06] cm2). FMT uptake at the putamen and caudate was significantly lower in iRBD patients with pathological SN hyperechogenicity compared with those without SN hyperechogenicity. However, no correlation was found between SN echogenicity and FMT uptake. This is in conflict with previous findings which showed that subjects with hyperechogenicity had lower FMT uptake in the striatum.

Conclusion

Pathological hyperechogenic alterations in the SN in patients with iRBD may suggest the existence of preclinical SN dysfunction as determined by FMT-PET.

Introduction

Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by dream-enacting behaviours, unpleasant dreams and lack of muscle atonia during REM sleep. RBD may be idiopathic or related to neurological disease [1]. Patients with idiopathic RBD (iRBD) have been reported to be at increased risk for developing Parkinson’s disease (PD) [2]. Transcranial sonography (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in patients with PD and in approximately 10% of healthy subjects, and has been suggested as a risk marker for PD in non-Parkinsonian subjects [3]. However, Berg et al. reported that SN hyperechogenicity in the elderly is non-specific and of limited usefulness in predicting an individual’s risk for PD [4]. Recently, two case-control studies [5], [6] showed that pathological SN hyperechogenicity was significantly more common in patients with iRBD compared to control subjects. iRBD is regarded as one of the non-motor symptoms of PD, and precedes motor symptoms. Schenck et al. identified the development of Parkinsonism in 11 of 29 men initially diagnosed with iRBD [7]. It is hypothesized that SN hyperechogenicity in healthy subjects and patients with iRBD is a vulnerability marker for PD. Although there is strong evidence that the echo originates from increased local iron content, the exact pathophysiological mechanisms for SN hyperechogenicity are not completely understood.

In order to verify the hypothesis that hyperechogenic alterations in the SN may be suggestive of preclinical nigrostriatal dopaminergic dysfunction for patients with iRBD, this study evaluated the presynaptic dopaminergic function in the striatum using 6-[18F] fluoro-meta-tyrosine (FMT) positron emission tomography (PET).

Section snippets

Methods

This study was performed in accordance with the Declaration of Helsinki. Procedures were approved by the Ethics Review Committee of Dokkyo Medical University, and informed consent was obtained from each subject. TCS and 6-[18F]FMT PET were performed in 19 males with iRBD confirmed by polysomnography. The mean age of subjects was 66.4 (standard deviation [SD] 4.9) years, the mean estimated duration of RBD was 3.5 (SD 1.8) years, the mean score on the Mini-Mental State Examination (MMSE) was 28.4

Results

Demographic and clinical data on patients with iRBD are summarized in Table 1. Nine of the patients with iRBD had pathological SN hyperechogenicity (mean 0.31 [SD 0.12] cm2) and 10 did not have SN hyperechogenicity (mean 0.11 [SD 0.06] cm2). Therefore, the 19 patients were divided into two groups: those with and those without SN hyperechogenicity. Age distributions, MMSE scores, and UPDRS part III scores did not differ significantly between the groups. Evaluation of motor activity using the

Discussion

Unger et al. [12] identified a significant association between midbrain hyperechogenicity and iRBD, and reported that two out of five iRBD patients with SN hyperechogenicity had unremarkable findings by presynaptic dopamine transporter imaging with fluoropropyl-carbomethoxy-iodophenyl-tropane (FP-CIT) single-photon emission computed tomography (SPECT). Iranzo et al. [13] recently reported that 123I-FP-CIT striatal binding did not correlate with the extent of SN echogenicity in patients with

Financial disclosure

This work was supported by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.03.024.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

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Acknowledgements

The authors wish to thank their colleagues, particularly Y. Inoue (Japan Somnology Centre, Neuropsychiatry Research Institute and Department of Somnology, Tokyo Medical University). The authors also thank Dr. Masaya Segawa (Segawa Neurological Clinic for Children) for reviewing and commenting on the manuscript, and Junichi Saitou and Toshihiko Satou (PET Centre, Utsunomiya Central Clinic) for their technical support in performing FMT-PET.

References (20)

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