REM behavior disorder (RBD) can be one of the first symptoms of childhood narcolepsy

More than one in three adult patients suffering from narcolepsy-cataplexy experience rapid eye movement (REM) behavior disorder (RBD), while RBD in childhood is extremely rare. We present the cases of two girls (aged 9 and 7 years old) with narcolepsy-cataplexy, in whom RBD was one of the first symptoms of the disease. The coincidence of RBD was seen by nocturnal video-polysomnography (v-PSG), and narcolepsy was diagnosed from short sleep latency and multiple sleep onset REMs (SOREMs) during a multiple sleep latency test (MSLT). Both girls were human leukocyte antigen (HLA)-DQB1 *0602 positive, and their cerebrospinal fluid (CSF) hypocretin level (Hcrt-1) was extremely low.     

Mirtazapine induces REM sleep behavior disorder (RBD) in parkinsonism

Shortly after initiation of mirtazapine (a noradrenergic and serotonergic antidepressant) treatment in four patients with parkinsonism, the authors observed the appearance of REM sleep behavior disorder (RBD). In the two patients with severe motor symptoms, RBD was accompanied by hallucinations and confusion. These disturbances resolved with drug discontinuation, and remained resolved by 12- to 24-month follow-up, suggesting that RBD can be triggered by a drug lacking anticholinergic activity.     

Motor dyscontrol in narcolepsy: rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder.

Narcolepsy involves abnormalities of rapid-eye-movement (REM) sleep, including a short latency to the onset of REM sleep, hypnagogic hallucinations, and sleep paralysis. In addition, persistence of muscle tone by electromyographic criteria or excessive muscle twitching during REM sleep or both have been reported in treated and untreated narcoleptic patients. We report that another previously described abnormality of REM sleep, REM sleep behavior disorder, may also be a symptom of narcolepsy. This disorder was found in 10 narcoleptic patients during routine clinical evaluations involving polysomnography and multiple sleep latency tests. During REM sleep, 7 additional narcoleptic patients displayed persistent muscle tone and/or excessive twitching, which we believe to be subclinical components of REM sleep behavior disorder. These 17 patients, diagnosed by established criteria for narcolepsy and for REM sleep behavior disorder, ranged in age from 8 to 74 years. Seventy-one percent were male. Narcolepsy and REM sleep behavior disorder most commonly emerged in tandem. In 3 patients, treatment of narcolepsy-cataplexy with stimulants and tricyclics either induced or exacerbated REM sleep behavior disorder.     

From bench to bed: putative animal models of REM sleep behavior disorder (RBD)

REM behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia, leading to abnormal and potentially injurious behavior during REM sleep. It is considered one of the most specific predictors of neurodegenerative disorders, such as Parkinson’s disease. In this paper, we provide an overview of animal models contributing to our current understanding of REM-associated atonia, and, as a consequence, the pathophysiology of RBD. The generator of REM-associated atonia is located in glutamatergic neurons of the pontine sublaterodorsal nucleus (SLD), as shown in cats, rats and mice. These findings are supported by clinical cases of patients with lesions of the homologous structure in humans. Glutamatergic SLD neurons, presumably in conjunction with others, project to (a) the ventromedial medulla, where they either directly target inhibitory interneurons to alpha motor neurons or are relayed, and (b) the spinal cord directly. At the spinal level, alpha motor neurons are inhibited by GABAergic and glycinergic interneurons. Our current understanding is that lesions of the glutamatergic SLD are the key factor for REM sleep behavior disorder. However, open questions remain, e.g. other features of RBD (such as the typically aggressive dream content) or the frequent progression from idiopathic RBD to neurodegenerative disorders, to name only a few. In order to elucidate these questions, a constant interaction between basic and clinical researchers is required, which might, ultimately, create an early therapeutic window for neurodegenerative disorders.     

REM sleep behaviour disorder (RBD) and its associations in young patients

Study objectivesTo retrospectively examine the characteristics of a population of patients <50 years of age with clinical and polysomnographic features diagnostic for RBD.MethodsReview of our sleep centre’s database for patients with RBD diagnosed over the last 7 years. Ninety-one patients were separated into two groups according to their age at the time of diagnosis (<50 y and ?50 y). Clinical and polysomnographic data were reviewed.ResultsSixty-two were male; mean age was 52 ± 19 y. Thirty-nine were <50 y. In the group <50 y there was a male predominance but in a smaller proportion (M:F = 1.4:1) compared with the group ?50 (M:F = 3:1). Seventy-six patients complained of abnormal behaviour (AB) during sleep, 12 with narcolepsy complained of excessive daytime sleepiness (EDS) with the AB being elicited only during consultation, and three complained of both EDS and AB. All patients, except one in the group ?50, described AB related to vivid dreams with violent content. The majority of the patients had the idiopathic form of RBD in both groups (51.2% group <50, 63.4% group ?50). The secondary form was associated with narcolepsy in 38.4% of patients in the group <50 y and with a synucleinopathy in 28.8% of patients in the group ?50. A strong association was noted between RBD and non-REM parasomnias.ConclusionsIn a population of patients with RBD presenting to a regional sleep laboratory, more than one-third of patients were <50 y at time of diagnosis. The commonest associated disorder was narcolepsy in patients <50 y, and synucleinopathy in those ?50 y. The coexistence of RBD with a NREM parasomnia was not uncommon in cases of idiopathic RBD affecting patients <50 y.     

The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known. In the present review, we present the most recent results on the neuronal network responsible for PS. Based on these results, we propose an updated integrated model of the mechanisms responsible for PS and explore different hypotheses explaining RBD and cataplexy. We propose that RBD is due to a specific degeneration of a sub-population of PS-on glutamatergic neurons specifically responsible of muscle atonia, localized in the caudal pontine sublaterodorsal tegmental nucleus (SLD). Another possibility is the occurrence in RBD patients of a specific lesion of the glycinergic/GABAergic pre-motoneurons localized in the medullary ventral gigantocellular reticular nucleus. Conversely, cataplexy in narcoleptics would be due to the activation during waking of the caudal PS-on SLD neurons responsible for muscle atonia. A phasic glutamatergic excitatory pathway from the central amygdala to the SLD PS-on neurons activated during emotion would induce such activation. In normal conditions, the glutamate excitation would be blocked by the simultaneous excitation by the hypocretins of the PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus, gating the activation of the PS-on SLD neurons.     

Case Report of Rapid-eye-movement(REM) sleep behavior disorder

Summary

A 23-year-old female student presented with a five-year history of abnormal sleep in which she would sit up or stand up for brief periods in the early morning, talk loudly for a couple of minutes and then lie back down. When woken by family members she would remember vivid dreams and nightmares. In one episode she had a fall that resulted in a subdural hematoma. On presentation at the psychiatric hospital she had a normal mental status exam except for being mildly depressed and anxious about the chronic fatigue from poor sleep. Overnight polysomnography (PSG) showed multiple waking periods each night, poor sleep efficiency and a lack of normal muscle paralysis during REM sleep. The patient was diagnosed with REM Sleep Behavior Disorder and treated with 1 mg clonazepam nightly. Her sleep improved dramatically and remained better at a six-month follow-up, but repeat PSG exam found that the lack of muscle paralysis during REM sleep remained.     

The relation between abnormal behaviors and REM sleep microstructure in patients with REM sleep behavior disorder

ObjectiveTo investigate the temporal relation between rapid eye movement (REM) sleep microstructure (REMs, EMG activity) and motor events in REM sleep behavior disorder (RBD).MethodsPolysomnographic records of eight patients with RBD were analyzed and compared with those of eight sex- and age-matched controls. We examined sleep microstructure for REM sleep with and without REMs and phasic chin EMG activity and their temporal relation to motor events on video.ResultsAll types of motor events were either more frequent in RBD patients than in controls (P ? 0.007) or present solely in RBD patients. In RBD, major motor events were significantly more frequent during REM sleep with REMs than during REM sleep without REMs (violent, 84.0% vs. 16.0%, P < 0.001; complex/scenic behavior, 78.1% vs. 23.2%, P < 0.001; major jerks, 77.5% vs. 20.3%, P < 0.001), whereas minor motor activity was evenly distributed (54.1% vs. 45.9%, P = 0.889). Controls showed predominantly minor motor activity with rare myoclonic body jerks. The distribution of motor events did not differ between REM sleep with and without REMs (40.9% vs. 59.1%, P = 0.262).ConclusionsIn RBD, major motor activity is closely associated with REM sleep with REMs, whereas minor jerks occur throughout REM sleep. This finding further supports the concept of a dual nature of REM sleep with REMs and REM sleep without REMs and implies a potential gate control mechanism of REM sleep with REMs for the manifestation of elaborate or violent behaviors in RBD.     

Validation of the MDS research criteria for prodromal Parkinson's disease: Longitudinal assessment in a REM sleep behavior disorder (RBD) cohort

Background : Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies. Methods : This prospective cohort study was performed on 121 individuals with rapid eye movement sleep behavior disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post‐test probability of the criteria were calculated at baseline and during each follow‐up visit. Results : Forty‐eight (39.7%) individuals with rapid eye movement sleep behavior disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4‐year follow‐up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair‐wise combinations of different prodromal markers showed that markers were independent of one another. Conclusion : The prodromal criteria are a promising tool for predicting incidence of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep behavior disorder cohort, with high sensitivity and high specificity with long follow‐up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria. © 2017 International Parkinson and Movement Disorder Society     

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = ?25.7 ± 13.0 mmHg vs. ?4.9 ±14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease‐specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked. © 2008 Movement Disorder Society     

Relation between subtype of Parkinson's disease and REM sleep behavior disorder

OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently found in Parkinson's disease (PD). PD has been classified in different subtypes and it is unknown if RBD occurs more often in one particular subtype. METHODS: Determination of PD subtype by review of clinical history in consecutively diagnosed PD patients with RBD. RESULTS: We determined the subtype (tremor- or non-tremor-predominant) of PD and the age at onset of parkinsonism and RBD by review of clinical history. PD patients with RBD had mostly the non-tremor-predominant subtype. RBD preceded parkinsonism only when parkinsonism started after the age of 50 years. CONCLUSIONS: A different pattern of neurodegeneration in non-tremor-predominant PD may explain its preferential association with RBD. The neurodegeneration that causes PD might be insufficient to produce RBD before the sixth decade.     

A brainstem inflammatory lesion causing REM sleep behavior disorder and sleepwalking (parasomnia overlap disorder)

A 40-year-old woman with no prior parasomnia developed an acute inflammatory rhombencephalitis with multiple cranial nerve palsies and cerebellar ataxia, followed by myelitis 6 months later, and by an intracranial thrombophlebitis 1 month after. Between and after these episodes, she had a persistent, mild right internuclear ophtalmoplegia, a mild cerebellar ataxia, and a severe REM sleep behavior disorder (RBD) lasting for 2 years. She talked, sang and moved nightly while asleep, and injured her son (cosleeping with her) while asleep. In addition, she walked asleep nightly. During video-polysomnography, there were two arousals during slow wave sleep without abnormal behavior, while 44% of REM sleep was without chin muscle atonia with bilateral arm and leg movements. There were small hypointensities in the right pontine tegmentum and in the right dorsal medulla on T1-weighted magnetic resonance imaging, suggesting post-inflammatory lesions that persisted between acute episodes. The RBD and sleepwalking did not improve with clonazepam, but improved with melatonin 9 mg/d. The unilateral small lesion of the pontine tegmentum could be responsible for the parasomnia overlap disorder as in other rare lesional cases.     

Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK)

ObjectivesThere are limited screening instruments for diagnosis of REM sleep behavior disorder (RBD) and none for quantifying the severity of disease. We aimed to validate a 13-item self-reported RBD questionnaire (RBDQ-HK) for diagnostic and monitoring purposes.MethodsBased on ICSD-II and our previous clinical and empirical work, the RBDQ-HK questionnaire was designed and administered in patients attending university-affiliated sleep clinic and psychiatric out-patient clinic, and subjects from the general population. ROC curve and exploratory factor analysis were employed to evaluate the scale, which had a score ranging from 0 to 100.ResultsOne hundred and seven RBD patients [mean age 62.6 (15.5) years; male 70.1%] and 107 control subjects [mean age 55.3 (9.0) years, male 57.9%] completed the questionnaire. The diagnoses of all the study subjects were independently ascertained by clinical interview and PSG. RBD patients had a significantly higher total RBDQ-HK score [mean (s.d.): 32.1 (16.1), range 3–71] than the control group [9.5 (10.2), range 0–55] (p < 0.005). The RBDQ-HK demonstrated robust psychometric properties with moderate sensitivity (82.2%), specificity (86.9%), positive predictive value (PPV; 86.3%), and negative predictive value (NPV; 83.0%), high internal consistency and test–retest reliability. Exploratory factor analysis revealed two components (dream-related and behavioral factors) that corresponded to the essential clinical features of RBD. The best cut-off for total score (range 0–100) was at 18/19 and the best cut-off for factor 2 (behavioral factors including sleep talking, shouting, limb movements and sleep-related injuries, range 0–70) was at 7/8.ConclusionsThe RBDQ-HK has satisfactory validity and reliability as a measure of clinical RBD symptoms and severity. It may serve as an effective tool for diagnosis and evaluation of the disease course to facilitate future clinical and research studies.     

Development of scales for assessment of rapid eye movement sleep behavior disorder (RBD)

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by an absence of normal skeletal muscle atonia during REM sleep and clinical features of disturbing dreams and dream enacting behaviors. Hence, the common sequelae are sleep-related injury and violence to both patients and bed-partners. Although polysomnographic evidence of REM sleep without atonia, is regarded as a gold standard for the confirmation of RBD diagnosis, polysomnography is both time and resource consuming. In order to facilitate early detection and clinical management, developing a convenient and suitable screening tool to identify individuals at risk of RBD would enable physicians to prioritize those who may require timely assessment and clinical intervention. In addition, the longitudinal course of RBD and its prognostic implication in predicting neurodegenerative disorders may suggest a potential therapeutic window for early preventive management of underlying progress of neurodegeneration. The availability of suitable RBD scales may facilitate timely assessment, accurate diagnosis and monitoring of disease progress of RBD. The present paper summarized recent research on the development of screening tools of RBD, their psychometric properties, and the applications of these questionnaires.     

47例REM睡眠行为障碍分析

目的 分析REM睡眠行为障碍的临床表现,探讨其病因、发病机制和治疗方法 .方法 回顾性分析47例REM睡眠行为障碍患者的病历资料.结果 47例患者均为中、老年人,均在熟睡过程中突然出现表现多样的行为障碍,多导睡眠图均为REM睡眠期出现肌弛缓现象消失而伴随肌电活动;病因为5例为帕金森病,3例为酒精戒断,1例为脑外伤,2例多系统萎缩,4例为药物滥用,32例为原发性;治疗应用氯硝西泮,或/和卡马西平、左旋多巴,所有患者有效.结论 REM睡眠行为障碍病因复杂、临床表现多样,经过合理药物、心理治疗,可以取得理想的治疗效果.