Medline ® Abstracts for References 55,59,60

OBJECTIVE: To describe the clinical phenotype of idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) at presentation in a sleep center.

METHODS: Clinical history review of 203 consecutive patients with IRBD identified between 1990 and 2014. IRBD was diagnosed by clinical history plus video-polysomnographic demonstration of REM sleep with increased electromyographic activity linked to abnormal behaviors.

RESULTS: Patients were 80% men with median age at IRBD diagnosis of 68 y (range, 50-85 y). In addition to the already known clinical picture of IRBD, other important features were apparent: 44% of the patients were not aware of their dream-enactment behaviors and 70% reported good sleep quality. In most of these cases bed partners were essential to convince patients to seek medical help. In 11% IRBD was elicited only after specific questioning when patients consulted for other reasons. Seven percent did not recall unpleasant dreams. Leaving the bed occurred occasionally in 24% of subjects in whom dementia with Lewy bodies often developed eventually. For the correct diagnosis of IRBD, video-polysomnography had to be repeated in 16% because of insufficient REM sleep or electromyographic artifacts from coexistent apneas. Some subjects with comorbid obstructive sleep apnea reported partial improvement of RBD symptoms following continuous positive airway pressure therapy. Lack of therapy with clonazepam resulted in an increased risk of sleep related injuries. Synucleinopathy was frequently diagnosed, even in patients with mild severity or uncommon IRBD presentations (e.g., patients who reported sleeping well, onset triggered by a life event, nocturnal ambulation) indicating that the development of a neurodegenerative disease is independent of the clinical presentation of IRBD.

CONCLUSIONS: We report the largest IRBD cohort observed in a single center to date and highlight frequent features that were not reported or not sufficiently emphasized in previous publications. Physicians should be aware of the full clinical expression of IRBD, a sleep disturbance that represents a neurodegenerative disease.

COMMENTARY: A commentary on this article appears in this issue on page 7.

REM sleep behaviour disorder (RBD) is an injurious clinical disorder of attempted dream-enactment ('oneirism') in humans which has a corresponding experimental animal model involving dorsolateral pontine tegmental lesions in cats. To date, our sleep disorders centre has collected data on 96 chronic RBD cases which can be compared with pooled data on 70 chronic RBD cases from other centres contained in 26 reports published in the world literature since 1985, when our initial cases were first reported. The data from our centre and from other centres demonstrate a male predominance in RBD (87.5% vs 63.5%); indicate a similar mean age of RBD onset (52.4 y vs 55.9 y); contain substantial numbers of diverse central nervous system disorders causally associated with RBD (47.9% vs 60.0%); and identify clonazepam treatment as being very effective in controlling both the (violent) dream and sleep behavioural disturbances of RBD. Our centre's data additionally reveal an 80% prevalence of elevated stage 3/4 (slow-wave) sleep% for age in RBD, and reveal a frequent presence of periodic and aperiodic limb movements during NREM sleep. Thus, RBD in humans is a complex syndrome in which there is generalized REM and NREM sleep motor dyscontrol, as was originally observed in the animal RBD model by Jouvet and Delorme in 1965.

We describe demographic, clinical, laboratory and aetiological findings in 93 consecutive patients with rapid eye movement (REM) sleep behaviour disorder (RBD), which consists of excessive motor activity during dreaming in association with loss of skeletal muscle atonia of REM sleep. The patients were seen at the Mayo Sleep Disorders Center between January 1, 1991 and July 31, 1995. Eighty-one patients (87%) were male. The mean age of RBD onset was 60.9 years (range 36-84 years) and the mean age at presentation was 64.4 years (37-85 years). Thirty-two per cent of patients had injured themselves and 64% had assaulted their spouses. Subdural haematomas occurred in two patients. Dream content was altered and involved defence of the sleeper against attack in 87%. The frequency of nocturnal events decreased with time in seven untreated patients with neurodegenerative disease. MRI or CT head scans were performed in 56% of patients. Although four scans showed brainstem pathology, all of these patients had apparently unrelated neurodegenerative diseases known to be associated with RBD. Neurological disorders were present in 57% of patients; Parkinson's disease, dementia without parkinsonism and multiple system atrophy accounted for all but 14% of these. RBD developed before parkinsonism in 52% of the patients with Parkinson's disease. Five of the 14 patients with multiple system atrophy were female, and thus the strong male predominance in RBD is less evident in this condition. Psychiatric disorders, drug use or drug withdrawal were rarely causally related to RBD. Clonazepam treatment of RBD was completely or partially successful in 87% of the patients who used the drug. We conclude that RBD is a well-defined condition and that descriptions from different centres are fairly consistent. It is commonest in elderly males and may result in serious morbidity to patients and bed partners. There is a strong relationship to neurodegenerative disease, especially Parkinson's disease, multiple system atrophy and dementia, and neurologists should explore the possibility of RBD in patients with these conditions. RBD symptoms may be the first manifestations of these disorders and careful follow-up is needed. Neuroimaging is unlikely to reveal underlying disorders not suspected clinically. We confirm the effectiveness of clonazepam, but note that attention to the safety of the bed environment may be sufficient for patients with contraindications to the drug.