Clinical reviewBrain imaging findings in idiopathic REM sleep behavior disorder (RBD) – A systematic review on potential biomarkers for neurodegeneration
Introduction
Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of physiological atonia of skeletal muscles during dreaming. This results in abnormal nocturnal behavior, such as flailing, punching, kicking and vocalization, self-inflicted injuries or injuries of bed partners ∗[1], [2], [3]. According to the International classification of sleep disorders (ICSD-3, 2014) the diagnosis of RBD requires the absence of atonia on electromyography (EMG) during REM sleep with excessive amounts of sustained or intermittent elevation of submental EMG tone or excessive phasic submental or upper or lower limb EMG twitching during polysomnography. Moreover, the exclusion of electroencephalographic epileptiform activity during REM sleep is a prerequisite for the diagnosis [4].
Over the past years, it has increasingly been recognized that RBD is associated with neurodegenerative diseases, particularly with the α-synucleinopathies Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB; ∗[1], [2], [5], [6], [7]). Assumed to be an initial symptom of progressive neurodegeneration, RBD can precede the clinical manifestation of these diseases by many years with risk estimates of up to 33% at 5 y, 76% at 10 y and 91% at 14 y after RBD diagnosis [8], [9]. However, individual prognoses concerning the risk of subsequent phenoconversion and likelihood to develop a specific α-synucleinopathy are challenging. Therefore, an increasing number of studies are seeking to establish neuroimaging markers to detect neurodegenerative brain changes at the earliest possible stage. We summarize recent advances in brain imaging in RBD and provide recommendations for the application of currently available neuroimaging modalities to monitor disease progression.
Section snippets
Methods
We ran electronic searches for English peer-reviewed journal articles indexed in the PubMed database until February 2016. The following keywords were used for search: “REM sleep behavior disorder OR RBD” AND “imaging; neuroimaging; transcranial sonography; TCS; PET; SPECT; MRI OR MRS”. To identify additional studies that were not retrieved in this initial search, we browsed through reference lists and published reviews focusing on this or similar topics. Only studies on idiopathic RBD without
Radiotracer imaging
Positron emission tomography (PET) and single photon emission computerized tomography (SPECT) in combination with a variety of radiotracers can be used to explore striatal dopaminergic integrity, brain metabolism and brain perfusion (for a detailed review see [12]). Table 2 provides an overview of the studies on radiotracer imaging in RBD that met our inclusion criteria. The major findings are summarized below.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) assesses brain structure and function without exposing subjects to ionizing radiation. It has been applied in several studies on functional and structural brain changes in RBD (Table 3) with novel sequences allowing for the investigation of brain metabolism, microstructure and iron content.
Transcranial sonography
Transcranial sonography (TCS) visualizes echogenicity of brain tissue. SN hyperechogenicity is reported in the majority of PD patients [77] and the risk for subsequent PD has been shown to be significantly increased in individuals with hyperechogenic compared to normechogenic SN in a 3-y multicenter follow-up study of 1847 elderly [78]. Moreover, TCS has been proposed to be useful in the differential diagnosis of parkinsonian syndromes [77].
Several studies have applied TCS in RBD (Table 4).
Conclusions
Over the past years neuroimaging has enhanced our understanding of RBD pathophysiology and its association with α-synucleinopathies. Although there is no gold standard, an increasing number of studies have provided encouraging results suggesting that various imaging modalities can augment the assessment of RBD progression and allow for the identification of individuals at risk for subsequent phenoconversion to progressive neurodegenerative disease.
Imaging of presynaptic dopaminergic function
Conflicts of interest
The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
Acknowledgments
KR was partly funded by the German Federal Ministry of Education and Research (BMBF 01GQ1402) and Alzheimer Forschung Initiative e.V. (AFI 13812). The position of JH was supported by the START-Program of the Faculty of Medicine at the RWTH Aachen University, Germany (23/12 to KR).
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