Diffusion Tensor Imaging in Idiopathic REM Sleep Behavior Disorder Reveals Microstructural Changes in the Brainstem, Substantia Nigra, Olfactory Region, and Other Brain Regions

Unger, Marcus M.; Belke, Marcus; Menzler, Katja; Heverhagen, Johannes T.; Keil, Boris; Stiasny‐Kolster, Karin; Rosenow, Felix; Diederich, Nico J.; Mayer, Geert; Möller, Jens Carsten; Oertel, Wolfgang H.; Knake, Susanne

doi:10.1093/sleep/33.6.767

Cited by 173 publications

(120 citation statements)

References 55 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Lesions in glycinergic/GABAergic brainstem regions elicit RBD-like motor behaviors in cats and rats (Schenkel and Siegel, 1989;Holmes and Jones, 1994;Lu et al, 2006). Further, microstructural changes in inhibitory brainstem circuitry are associated with human RBD (Kimura et al, 2000;Tippmann-Peikert et al, 2006;Unger et al, 2010). We assert that reduced CNS inhibition could therefore underlie REM motor behaviors in RBD.…”

Section: Impaired Inhibitory Transmission Triggers Rbd Motor Symptomsmentioning

confidence: 80%

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

Brooks¹,

Peever²

2011

J. Neurosci.

112

View full text Add to dashboard Cite

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.

show abstract

Section: Impaired Inhibitory Transmission Triggers Rbd Motor Symptomsmentioning

confidence: 80%

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

Brooks¹,

Peever²

2011

J. Neurosci.

112

View full text Add to dashboard Cite

show abstract

“…3,4 Previous studies have shown that basal ganglia structures, such as the substantia nigra pars reticulata and the internal segment of the globus pallidus, have caudal connections to regions that modulate REM sleep atonia. 5 Imaging studies in iRBD patients have shown microstructural changes in substantia nigra, 6 reduced volume of the putamen, 7 as well as reduced density of the striatal dopamine transporter, which decreases in the course of disease progression. 8 In addition monkeys treated sub-chronic with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), a neurotoxin which specifically targets dopaminergic neurons of the substantia nigra pars compacta via uptake by the dopamine transporter, show an increase in the number of sleep epochs with high-amplitude EMG bouts during REM sleep compared to control animals.…”

Section: Introductionmentioning

confidence: 99%

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

Zoetmulder

Nikolic

Biernat

et al. 2016

Journal of Clinical Sleep Medicine

View full text Add to dashboard Cite

Study Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. Methods: 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omegafluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ( 123 I-FP-CIT SPECT), neurological examination, and polysomnography. Results: iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls.123 I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to 123 I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Conclusions: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. I NTRO DUCTI O NREM sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia , dream enactment behavior, and vivid (and/or) violent dreams. Longitudinal studies have shown that patients with idiopathic RBD (iRBD) have an increased risk for developing an α-synucleinopathy, such as Parkinson disease (PD).1,2 The high proportion of iRBD patients developing PD may indicate a link between nigrostriatal degeneration and increased night-time motor activity. It is increasingly recognized that the dopaminergic system is associated with sleep-wake disturbances.3,4 Previous studies have shown that basal ganglia structures, such as the substantia nigra pars reticulata and the internal segment of the globus pallidus, have caudal connections to regions that modulate REM sleep atonia. 5 Imaging studies in iRBD patients have shown microstructural changes in substantia nigra, 6 reduced volume of the putamen, 7 as well as reduced density of the striatal dopamine transporter, which decreases in the course of disease progression. 8 In addition monkeys treated sub-chronic with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), a neurotoxin which specifically targets dopaminergic neurons of the substantia nigra...

show abstract

“…As a result of this predictable pattern of diffusion, which is orientation dependent (or anisotropic), location and orientation of white matter tracts can be determined. 6,13,14,33,34,50 Several articles have described the implementation of DTI for a multitude of neurological diseases and neuroanatomical studies; 8,10,14,22,38,42,50,58,59 however, none has addressed its specific application in the management of brainstem cavernous malformations (BSCMs).…”

mentioning

confidence: 99%

The utility of preoperative diffusion tensor imaging in the surgical management of brainstem cavernous malformations

Flores¹,

Whittemore

Samson³

et al. 2015

JNS

View full text Add to dashboard Cite

abbreviatioNs BSCM = brainstem CM; CM = cavernous malformation; CST = corticospinal tract; DTI = diffusion tensor imaging; DTT = diffusion tensor tractography; FA = fractional anisotropy; ICP = inferior cerebral peduncle; ML = medial lemniscus; MLF = medial longitudinal fasciculus; mRS = modified Rankin Scale. submitted April 9, 2013. accepted November 18, 2014. iNclude wheN citiNg Published online January 9, 2015; DOI: 10.3171/2014.11.JNS13680. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. obJect Resection of brainstem cavernous malformations (BSCMs) may reduce the risk of stepwise neurological deterioration secondary to hemorrhage, but the morbidity of surgery remains high. Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are neuroimaging techniques that may assist in the complex surgical planning necessary for these lesions. The authors evaluate the utility of preoperative DTI and DTT in the surgical management of BSCMs and their correlation with functional outcome. methods A retrospective review was conducted to identify patients who underwent resection of a BSCM between 2007 and 2012. All patients had preoperative DTI/DTT studies and a minimum of 6 months of clinical and radiographic follow-up. Five major fiber tracts were evaluated preoperatively using the DTI/DTT protocol: 1) corticospinal tract, 2) medial lemniscus and medial longitudinal fasciculus, 3) inferior cerebellar peduncle, 4) middle cerebellar peduncle, and 5) superior cerebellar peduncle. Scores were applied according to the degree of distortion seen, and the sum of scores was used for analysis. Functional outcomes were measured at hospital admission, discharge, and last clinic visit using modified Rankin Scale (mRS) scores. results Eleven patients who underwent resection of a BSCM and preoperative DTI were identified. The mean age at presentation was 49 years, with a male-to-female ratio of 1.75:1. Cranial nerve deficit was the most common presenting symptom (81.8%), followed by cerebellar signs or gait/balance difficulties (54.5%) and hemibody anesthesia (27.2%). The majority of the lesions were located within the pons (54.5%). The mean diameter and estimated volume of lesions were 1.21 cm and 1.93 cm 3 , respectively. Using DTI and DTT, 9 patients (82%) were found to have involvement of 2 or more major fiber tracts; the corticospinal tract and medial lemniscus/medial longitudinal fasciculus were the most commonly affected. In 2 patients with BSCMs without pial presentation, DTI/DTT findings were important in the selection of the surgical approach. In 2 other patients, the results from preoperative DTI/DTT were important for selection of brainstem entry zones. All 11 patients underwent gross-total resection of their BSCMs. After a mean postoperative follow-up duration of 32.04 months, all 11 patients had excellent or good outcome (mRS Score 0-3) at the time of last outpatient clinic evaluation. DTI score did not corre...

show abstract

Diffusion Tensor Imaging in Idiopathic REM Sleep Behavior Disorder Reveals Microstructural Changes in the Brainstem, Substantia Nigra, Olfactory Region, and Other Brain Regions

Cited by 173 publications

References 55 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

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

The utility of preoperative diffusion tensor imaging in the surgical management of brainstem cavernous malformations

Contact Info

Product

Resources

About