piperidines and REM-Sleep-Behavior-Disorder

To explore the neurochemical basis of REM sleep behavior disorder (RBD) in multiple-system atrophy (MSA).. In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of REM atonia loss by the percentage of REM sleep with tonically increased electromyographic (EMG) activity and the percentage of REM sleep with phasic EMG bursts. PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) was employed to measure the density of striatal monoaminergic terminals and SPECT with (-)-5-[123I]iodobenzovesamicol ([123I]IBVM) to measure the density of 123I]IBVM.. Age and gender distributions were similar in patient and normal control groups. The MSA subjects showed decreased mean [11C]DTBZ binding in the striatum (p < 0.0001) and decreased [123I]IBVM binding in the thalamus (p < 0.001). Moreover, in the MSA group, striatal [11C]DTBZ binding was inversely correlated with the severity of REM atonia loss (p = 0.003). Thalamic [123I]IBVM binding, however, was not correlated to the severity of REM atonia loss.. Decreased nigrostriatal dopaminergic projections may contribute to RBD in MSA.

Topics: Adult; Age Distribution; Aged; Binding, Competitive; Biogenic Monoamines; Carbon Radioisotopes; Corpus Striatum; Electromyography; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Multiple System Atrophy; Piperidines; Polysomnography; Predictive Value of Tests; Reference Values; REM Sleep Behavior Disorder; Sex Distribution; Tetrabenazine; Tetrahydronaphthalenes; Thalamus; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

The peripheral autonomic nervous system may be involved years before onset of motor symptoms in some patients with Parkinson's disease (PD). Specific imaging techniques to quantify the cholinergic nervous system in peripheral organs are an unmet need. We tested the hypothesis that patients with PD display decreased [. We included 15 PD patients and 15 age- and sex matched healthy controls for a 70 min whole-body dynamic positron emission tomography (PET) acquisition. Compartmental modelling was used for tracer kinetic analyses of adrenal gland, pancreas, myocardium, spleen, renal cortex, muscle and colon. Standard uptake values (SUV) at 60-70 min post injection were also extracted for these organs. Additionally, SUVs were also determined in the total colon, prostate, parotid and submandibular glands.. We found no statistically significant difference of [. [

Topics: Humans; Male; Parasympathectomy; Parkinson Disease; Piperidines; Positron-Emission Tomography; REM Sleep Behavior Disorder

REM sleep behaviour disorder (RBD) occurs frequently in patients with synucleinopathies such as Parkinson's disease, dementia with Lewy body, or multiple system atrophy, but may also occur as a prodromal stage of those diseases; and is termed idiopathic RBD (iRBD) when not accompanied by other symptoms. Cholinergic degeneration of the mesopontine nuclei have been described in synucleinopathies with or without RBD, but this has not yet been explored in iRBD. We sought to assess cholinergic neuronal integrity in iRBD using PET neuroimaging with the. The sample included 10 participants evenly divided between healthy subjects and patients with iRBD. Polysomnography and PET imaging with FEOBV were performed in all participants. Standardized uptake value ratios (SUVRs) were compared between the two groups using voxel wise t-tests. Non-parametric correlations were also computed in patients with iRBD between FEOBV uptake and muscle tonic and phasic activity during REM sleep.. Compared with healthy participants, significantly higher FEOBV uptakes were observed in patients with iRBD. The largest differences were observed in specific brainstem areas corresponding to the bulbar reticular formation, pontine coeruleus/subcoeruleus complex, tegmental periacqueductal grey, and mesopontine cholinergic nuclei. FEOBV uptake in iRBD was also higher than in controls in the ventromedial area of the thalamus, deep cerebellar nuclei, and some cortical territories (including the paracentral lobule, anterior cingulate, and orbitofrontal cortex). Significant correlation was found between muscle activity during REM sleep, and SUVR increases in both the mesopontine area and paracentral cortex.. We showed here for the first time the brain cholinergic alterations in patients with iRBD. As opposed to the cholinergic depletion described previously in RBD associated with clinical Parkinson's disease, increased cholinergic innervation was found in multiple areas in iRBD. The most significant changes were observed in brainstem areas containing structures involved in the promotion of REM sleep and muscle atonia. This suggests that iRBD might be a clinical condition in which compensatory cholinergic upregulation in those areas occurs in association with the initial phases of a neurodegenerative process leading to a clinically observable synucleinopathy.

Topics: Aged; Brain; Case-Control Studies; Cholinergic Neurons; Dementia; Female; Humans; Male; Middle Aged; Parkinson Disease; Piperidines; Polysomnography; Positron-Emission Tomography; REM Sleep Behavior Disorder; Sleep, REM; Synucleinopathies

Here, we report a case of rapid eye movement sleep behavioural disorder in an elderly patient with dementia with Lewy bodies. Pretreatment polysomnography revealed atonia during rapid eye movement sleep, absence of sleep spindles and loss of slow-wave sleep. Administration of donepezil, an acetylcholinesterase inhibitor, markedly improved delusional symptoms and cognitive function. Pretreatment polysomnography performed after donepezil administration revealed a considerable number of sleep spindles. The effects of cholinergic modulation induced by donepezil seemed to cause remarkable improvement in mental status, incorporating associated with sleep spindles generated by the thalamocortical circuit involved in this patient.

Topics: Aged, 80 and over; Cholinesterase Inhibitors; Cognition; Donepezil; Female; Humans; Indans; Lewy Body Disease; Piperidines; Polysomnography; Psychiatric Status Rating Scales; REM Sleep Behavior Disorder; Sleep, REM; Treatment Outcome

Dementia with Lewy bodies (DLB) is often associated with REM sleep behavior disorders (RBD) characterized, in contrast to the usual paralysis of REM sleep, by violent motor and verbal activity.. The pharmacological management of RBD was investigated in three DLB patients treated with clonazepam, a benzodiazepine used as an antiepileptic, or donepezil, a cholinesterase inhibitor.. All three patients had marked improvement. The pharmacodynamic mechanisms underlying the efficacy of the two drugs might be due to facilitator effect on the pedunculopontine nucleus, a key structure in the physiology of REM sleep.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Benzodiazepines; Cholinesterase Inhibitors; Clonazepam; Donepezil; Dose-Response Relationship, Drug; Female; Globus Pallidus; Humans; Indans; Lewy Body Disease; Locus Coeruleus; Male; Mental Status Schedule; Middle Aged; Nerve Net; Pedunculopontine Tegmental Nucleus; Piperidines; REM Sleep Behavior Disorder; Sleep-Wake Transition Disorders; Sleep, REM; Treatment Outcome; Violence

Three patients with REM behavior disorder whose nocturnal symptoms were markedly improved by treatment with the acetylcholinesterase inhibitor donepezil are reported. Donepezil may have a role in the treatment of REM behavior disorder, possibly through its actions on cholinergic pathways in the brainstem.

Topics: Adult; Aged; Cholinesterase Inhibitors; Donepezil; Humans; Indans; Male; Middle Aged; Piperidines; Polysomnography; REM Sleep Behavior Disorder