Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder

Eisensehr, Ilonka; Linke, R.; Noachtar, Soheyl; Schwarz, Johannes; Gildehaus, Franz-Josef; Tatsch, Klaus

doi:10.1093/brain/123.6.1155

Cited by 357 publications

(157 citation statements)

References 17 publications

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“…While there is no clear evidence that dopaminergics influence RBD symptoms (Iranzo et al, 2009a), imaging studies nonetheless indicate that dysfunction of the nigrostriatal dopamine system is associated with RBD (Albin et al, 2000;Eisensehr et al, 2000). We suggest that initial RBD onset is triggered by loss of GABAergic/glycinergic function and that progressive dopamine cell degeneration not only causes Parkinson's symptoms but also worsens RBD.…”

Section: Increasing Inhibitory Tone Improves Rbd Symptomsmentioning

confidence: 74%

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice

Brooks¹,

Peever²

2011

J. Neurosci.

116

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Rapid eye movement (REM) sleep behavior disorder (RBD) is a neurological disease characterized by loss of normal REM motor inhibition and subsequent dream enactment. RBD is clinically relevant because it predicts neurodegenerative disease onset (e.g., Parkinson's disease) and is clinically problematic because it disrupts sleep and results in patient injuries and hospitalization. Even though the cause of RBD is unknown, multiple lines of evidence indicate that abnormal inhibitory transmission underlies the disorder. Here, we show that transgenic mice with deficient glycine and GABA transmission have a behavioral, motor, and sleep phenotype that recapitulates the cardinal features of RBD. Specifically, we show that mice with impaired glycine and GABA A receptor function exhibit REM motor behaviors, non-REM muscle twitches, sleep disruption, and EEG slowing-the defining disease features. Importantly, the RBD phenotype is rescued by drugs (e.g., clonazepam and melatonin) that are routinely used to treat human disease symptoms. Our findings are the first to identify a potential mechanism for RBD-we show that deficits in glycine-and GABA A -mediated inhibition trigger the full spectrum of RBD symptoms. We propose that these mice are a useful resource for investigating in vivo disease mechanisms and developing potential therapeutics for RBD.

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Section: Increasing Inhibitory Tone Improves Rbd Symptomsmentioning

confidence: 74%

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice

Brooks¹,

Peever²

2011

J. Neurosci.

116

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“…22,23 Of note, the PDRP network has several advantages compared with dopaminergic imaging techniques. While PDRP expression is associated with both presynaptic nigrostriatal dopaminergic dysfunction and Unified Parkinson's Disease Rating Scale motor ratings, 6,24 it is worth noting that the magnitude of these correlations is modest.…”

Section: Logistical Regression Analysis Logistical Regression Analysismentioning

confidence: 99%

Abnormal metabolic network activity in REM sleep behavior disorder

et al. 2014

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Objective: To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion.Methods: For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 6 9.4 years old) and 10 healthy volunteers (62.7 6 8.6 years old) who underwent resting-state metabolic brain imaging with 18 F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 6 4.8 years old) and 17 healthy volunteers (66.6 6 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 6 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values.Results: PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p , 0.04; cohort 2: p , 0.005). Of the 17 subjects with long-term follow-up, 8 were diagnosed with Parkinson disease or dementia with Lewy bodies; the others did not phenoconvert. For individual subjects with RBD, final phenoconversion status was predicted using a logistical regression model based on PDRP expression and subject age at the time of imaging (r 2 5 0.64, p , 0.0001).Conclusions: Latent network abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.

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“…Using 123 I-IPT SPECT, Eisensehr et al found reduced striatal DAT binding in all 5 of their patients with idiopathic rapid-eye-movement sleep behavior disorder (64). In another series, 11 patients with sleep disorders were investigated with FP-CIT SPECT, and reduced striatal DAT binding was found in 3, 1 of whom had evidence of clinical parkinsonism (65).…”

Section: Detection Of Preclinical Pdmentioning

confidence: 99%

Imaging Approaches to Parkinson Disease

Brooks¹

2010

J Nucl Med

190

109

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Parkinson disease (PD) is associated with nigral degeneration and striatal dopamine deficiency. Demonstrating midbrain structural abnormalities with transcranial sonography or diffusionweighted MRI or showing striatal dopamine terminal dysfunction with PET or SPECT supports the diagnosis and rationalizes the use of dopaminergic medications. In atypical PD variants, transcranial sonography can detect striatal hyperechogenicity, and diffusion-weighted imaging can detect increased putamen water diffusion, whereas 18 F-FDG PET reveals reduced lentiform nucleus glucose metabolism. PET and SPECT can detect changes in striatal dopamine levels after levodopa administration and relate these to motor responses. Loss of cortical dopaminergic and cholinergic function is present in demented PD and, on occasion, amyloid deposits can be detected. Loss of cardiac sympathetic innervation can be sensitively detected in PD with 18 F-dopamine PET or 123 I-metaiodobenzylguanidine SPECT. Finally, PET can detect widespread brain inflammation in PD. This review discusses the role of structural and functional imaging for diagnosing and managing different parkinsonian syndromes.

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Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder

Cited by 357 publications

References 17 publications

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice

Abnormal metabolic network activity in REM sleep behavior disorder

Imaging Approaches to Parkinson Disease

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