Secondary REM Sleep Behavior Disorder Research Articles

The treatment efficacy of pharmacotherapies for rapid eye movement sleep behavior disorder with polysomnography evaluation: A systematic review and meta-analysis

Clonazepam and melatonin are commonly used as first-line medications for the treatment of rapid eye movement (REM) sleep behavior disorder (RBD), with other medications used in the clinic including pramipexole, ramelteon, and rotigotine. We performed a systematic review and meta-analysis of randomized and non-randomized controlled trials to assess the efficacy of these treatment options in RBD patients with polysomnography. We systematically retrieved results of randomized and non-randomized controlled trials using the PubMed, Embase, and Cochrane databases.Of the 454 studies identified, 13 were considered eligible for inclusion in the study. In comparison to baseline, clonazepam was found to significantly decrease the percentage of stage 2 sleep [4.00 (95% CI = 0.90 to 7.10)] in RBD patients. Melatonin was found to significantly improve patients’ sleep efficiency [2.51(95% CI = 0.75 to 4.28)], significantly reduce the time spent in bed (TIB) [−11.71(95% CI = −23.05 to −0.37)], phasic activity[−25.79(95% CI = −42.13 to −9.46)] and tonic activity[−10.44(95% CI = −12.24 to −8.64)]. RWA[−5.87 (95% CI = −8.25 to −3.50)] significantly improve with the use of ramelteon. Pramipexole was found to significantly increase the total sleep time (TST) [27.17 (95% CI = 0.06 to 54.29)], and significantly reduce the periodic limb movements of sleep (PLMS) index [−11.42(95% CI = −21.38 to −1.47)]. We also found that pramipexole had different effects on idiopathic RBD (iRBD) and secondary RBD (sRBD). These results will help to guide the clinical use of medication in patients with RBD.

Research progress in rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormal dream acting behavior such as vocalization and twitching related to dream content during REM sleep. The diagnosis requires polysomnography demonstrating a loss of normal skeletal muscle atonia during REM sleep. Both idiopathic RBD and secondary RBD are highly related to synucleinopathy including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Almost all idiopathic RBD patients will develop synucleinopathy after a few years. Therefore, RBD may be an early marker in the progression of synucleinopathy.

Trauma Immediately Preceding REM-Behavior Disorder: A Valuable Prognostic Marker?

Background: The definition of rapid eye movement (REM) sleep behavior disorder (RBD) has varied over the years. Rapid eye movement sleep behavior disorder can be considered isolated or idiopathic or can occur in the context of other disorders, including trauma-associated sleep disorder (TSD) and overlap parasomnia. However, whether trauma in RBD carries any prognostic specificity is currently unknown.Study Objectives: To test the hypothesis that RBD secondary to trauma is less likely to result in the development of neurodegeneration compared to idiopathic RBD (iRBD) without trauma in the general population.Methods: A retrospective cohort study of 122 consecutive RBD patients (103 males) at two tertiary sleep clinics in Europe between 2005 and 2020 was studied. Patients were diagnosed as having iRBD by video polysomnography (vPSG) and had a semi-structured interview at presentation, including specifically eliciting any history of trauma. Patients with secondary RBD to recognized causes were excluded from the study. Patients with iRBD were categorized into three groups according to reported trauma history: (1) No history of trauma, (2) traumatic experience at least 12 months prior to RBD symptom onset, and (3) traumatic experience within 12 months of RBD symptom onset. Idiopathic RBD duration was defined as the interval between estimated onset of RBD symptoms and last hospital visit or death. Follow-up duration was defined as the interval between iRBD diagnosis and last hospital visit or death.Results: In a follow-up period of up to 18 years, no patient who experienced trauma within 12 months preceding their iRBD diagnosis received a diagnosis of a neurodegenerative disorder (n = 35), whereas 38% of patients without trauma within the 12 months of symptom onset developed a neurodegenerative illness. These patients were also significantly more likely to have a family history of α-synucleinopathy or tauopathy.Conclusions: The development of RBD within 12 months of experiencing a traumatic life event, indistinguishable clinically from iRBD, did not lead to phenoconversion to a neurodegenerative disorder even after 18 years (mean follow up 6 years). We suggest that a sub-type of RBD be established and classified as secondary RBD due to trauma. Additionally, we advocate that a thorough psychological and trauma history be undertaken in all patients presenting with dream enactment behaviors (DEB).

Rapid Eye Movement Sleep Behavior Disorder and Other Rapid Eye Movement Sleep Parasomnias.

The most common rapid eye movement (REM) parasomnia encountered by neurologists is REM sleep behavior disorder (RBD), and nightmares are so frequent that every neurologist should be able to differentiate them from the dream enactment of RBD. Isolated sleep paralysis is relatively common and is often mistaken for other neurologic disorders. This article summarizes the current state of the art in the diagnosis of RBD, discusses the role of specific questionnaires and polysomnography in the diagnosis of RBD, and reviews recent studies on idiopathic RBD as an early feature of a synucleinopathy, secondary RBD, and its management. Recent diagnostic criteria and implications of nightmares and isolated sleep paralysis are also reviewed. Idiopathic RBD can now be considered as part of the prodromal stage of a synucleinopathy. Therefore, an accurate diagnosis is mandatory, and this implies detection of REM sleep without atonia. The polysomnography montage, including EMG of the submentalis and flexor digitorum superficialis muscles, provides a high sensitivity and specificity for the diagnosis. The exact diagnosis is important for patient counseling and for future neuroprotective trials. REM parasomnias include RBD, sleep paralysis, and nightmares, which have distinct clinical characteristics and different implications regarding diagnostic procedures, management, and prognosis.

Clinical Overview of REM Sleep Behavior Disorder.

AbstractRapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during REM sleep that allows motor responses to dream content. Patients display patterns of unusual, complex, and even violent motor activities. There is a high risk for harm to the patients or their bedpartners. REM sleep behavior disorder is more likely to occur in synucleinopathies such as Parkinson's disease, Lewy body dementia, and multiple system atrophy and may precede clinical manifestations by decades. In secondary RBD, brainstem centers involved in muscle atonia during REM are disrupted. These conditions include multiple sclerosis, cerebral vascular accidents, and brainstem tumors. The acute onset of RBD may associate with the use of antidepressants and acute withdrawal from alcohol. The diagnosis of RBD should be confirmed by polysomnography utilizing multiple-limb electromyography and synchronized digital video monitoring and demonstrate elevation of muscle tone during REM sleep along with dream enactment behavior. The differential diagnosis includes sleepwalking, nocturnal seizures, sleep apnea, and periodic limb movement disorder. Management focuses on maximizing safety, use of clonazepam/melatonin, and discussion of prognosis with patients.

An Open-Labeled Trial of Ramelteon in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia and elaborate motor activity in association with dream mentation. The melatonin receptor agonist ramelteon has been documented as being effective in two patients with secondary RBD. However, there are no reports on ramelteon treatment for idiopathic RBD. In an open-labeled trial, we treated 12 consecutive patients with idiopathic RBD for at least 4 w with 8 mg ramelteon given within 30 min before bedtime. Ramelteon treatment did not have a clear effect on REM sleep without atonia or an RBD severity scale measured by video-supported polysomnography. However, clinical assessment using a visual analog scale showed a trend toward significance and there were also definitely positive changes in some individual cases. Ramelteon was well tolerated in most patients, with minor side effects. Considering that ramelteon is associated with few side effects, further study may ascertain whether patients with RBD could be effectively treated by ramelteon, especially when clonazepam may not be suitable due to its side effects. A commentary on this article appears in this issue on page 643.

Gender differences in REM sleep behavior disorder: a clinical and polysomnographic study in China

ObjectiveRapid eye movement (REM) sleep behavior disorder (RBD) has been considered a male-predominant parasomnia, and there is little comparative data on potential differences between males and females. Therefore, the aim of our study was to examine and characterize gender difference in RBD. MethodsNinety patients diagnosed with RBD were consecutively recruited from a sleep medicine clinic. All patients were assessed by a RBD questionnaire and overnight video polysomnography. Demographic, clinical data, presence of dreams and dream-enacting behaviors, sleep parameters and electromyographic (EMG) activity were compared for male and female patients with RBD. ResultsFemales were significantly younger than males, both in the mean age of RBD onset (45.3 ± 19.3 vs. 56.2 ± 14.1; p = 0.027) and the mean age at diagnosis (50.4 ± 18.2 vs. 61.1 ± 14.1; p = 0.022). Secondary RBD was 21% in males and 44% in females (p = 0.021). Antidepressant use was more common among females (22%) than males (2%; p = 0.003). There was no significant gender difference in dream content (eg, violent and frightening dreams) of RBD patients. However, females had less dream-enacting behaviors, especially in movement related dreams and falling out of bed. Interestingly, no significant difference was found in the quantification of EMG activity during REM sleep between male and female patients. ConclusionsWe found significant gender differences in demographics, associated comorbidities, and dream-related behaviors in patients with RBD. Female RBD patients reported significantly less behavior during dreams, but there was no significant gender difference in EMG activity during REM sleep.

Use of Ramelteon for the Treatment of Secondary REM Sleep Behavior Disorder

We used ramelteon to treat two patients with secondary REM sleep behavior disorder (RBD) complications along with neurodegenerative diseases including multiple system atrophy and Parkinson's disease. These two patients not only improved in terms of their clinical RBD symptoms but also exhibited a decrease in the proportion of REM sleep without atonia (from 8.5% to 3.5% and from 10.9% to 3.9% in the two patients). Although clonazepam is the standard first-line therapy for the treatment of RBD, ramelteon might be an effective treatment alternative in patients with RBD who cannot take clonazepam due to either ineffectiveness or adverse effects.

Idiopathic REM sleep behavior disorder as a long-term predictor of neurodegenerative disorders

REM sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behavior and loss of muscle atonia during REM sleep. Idiopathic RBD occurs in the absence of any neurological disease or other possible cause, is male-predominant and its clinical course is generally chronic progressive. Secondary RBD may be related to neurodegenerative disorders such as multiple system atrophy, Parkinson’s disease and Lewy body dementia. Recent long-term prospective studies have shown that 30% to 65% of patients with idiopathic RBD will eventually develop a neurodegenerative disorder with the rate of emergence depending on the length of the follow-up period. RBD may therefore be one of the earliest signs of and/or a long-term predictor for neurodegenerative disorders. Because RBD antecedes the development of these disorders by several years or decades, its recognition may enable the delay or prevention of neurodegenerative disorders through the early application of neuroprotective or disease-modifying therapies in the future.

An Angry Bed Partner

A 59-year-old man presented with the concern that his wife had witnessed him stopping breathing while asleep. Review of his sleep history also revealed agitated behaviors occurring during sleep. He reported almost nightly episodes of flailing his arms and legs about, often accompanied by angry yelling. When awoken from these episodes by his wife, he had clear dream recall, usually involving being in an argument or a fight with someone. His wife had resorted to sleeping in another bed so as not to be harmed. He had to date not suffered serious injury from one of these episodes. These behaviors were first noticed at 30 years of age. His past medical history included depression, hypertension, coronary artery disease and hypercholesterolemia, for which he took fluoxetine, clopidogrel, atenolol, ezetimibe/simvastatin, lisinopril, aspirin, and a multivitamin. Neurologic and systemic examinations were normal. There was no family history of neurodegenerative disease. Polysomnography with time-synchronized audiovisual monitoring and an expanded EEG montage showed mild OSA, with an AHI of 5. REM sleep was notable for persistent muscle tone recorded using 3 chin EMG leads. Overt yelling (“you want trouble, then keep it shut”) and swinging of the arms in a punching motion were recorded on video during REM sleep as well. An example of his REM sleep is shown in Figure 1. Figure 1 30-second epoch tracing of polysomnography recorded during REM sleep reveals persistent chin EMG tone during REM sleep, with overt whole-body movements at the end of the epoch. LEOG = Left electrooculogram, REOG = Right electrooculogram, FP1A2 – ... How would you treat this patient? Withdrawal of fluoxetine with careful psychiatric monitoring. REM sleep behavior disorder (RBD) is a REM-sleep parasomnia characterized by a lack of generalized atonia during REM sleep. Clinically, this usually presents as pronounced activity during sleep accompanied by vivid dream recall when awoken. Most often, the dream content is violent or anxious in nature.1 RBD may be idiopathic or secondary, being associated with neurodegenerative diseases, narcolepsy, cerebrovascular disease, intracranial tumors, central nervous system infection, and medication use. In particular, selective serotonin reuptake inhibitors, including fluoxetine, have been shown to cause secondary RBD.2 After a careful review of the patient's medication history, it was found that the RBD symptoms began around the time he had started taking fluoxetine 40 mg daily for severe depression symptoms. Therefore, secondary RBD (to fluoxetine) was suspected due to the start of symptoms with the start of fluoxetine therapy. Fluoxetine had fully controlled his depression symptoms during 19 years of continuous therapy. Two options were considered to treat the patient's RBD: addition of clonazepam, or withdrawal of fluoxetine with careful monitoring. The patient chose the latter option, and weaning was performed with close outpatient monitoring of his depressive symptoms. His RBD symptoms resolved around 6 weeks after discontinuation of fluoxetine, and a repeat polysomnogram was performed 3 months later. A representative REM sleep epoch is shown in Figure 2, showing a restoration of appropriate atonia in REM. The patient's clinical course demonstrates a more rapid response to withdrawal of fluoxetine compared to the original case report of this association, a major difference between the cases being patient age.2 There was a recurrence of depressive symptoms four months after discontinuing fluoxetine, and the patient was treated with bupropion, a dopaminergic/noradrenergic antidepressant without any reported tendency to induce or aggravate RBD.3 Bupropion therapy did not result in recurrence of RBD symptoms. Figure 2 0-second epoch tracing of polysomnography recorded during REM sleep shows normal reduction of EMG tone during REM sleep 3 months after fluoxetine discontinuation. LEOG = Left electrooculogram, REOG = Right electrooculogram, FP1A2 – O2A2 = Electroencephalogram ... The possibility of obstructive sleep apnea (OSA) triggering the RBD symptoms was entertained.4 Given the mild nature of the OSA, the polysomnographic findings, and the clinical response to fluoxetine withdrawal, this was not considered a major factor in this case. The patient's OSA was treated with positional therapy, and he and his wife were able to return to sleeping in the same bed with improvement in both his OSA and RBD symptoms.

Slow‐wave sleep and delta power in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by the loss of normal muscle atonia during REM sleep, leading to an increase of phasic muscle activity and complex motor behaviors during the night. There is some evidence that RBD patients have more of slow-wave sleep (SWS) than healthy elderly subjects. No study has looked at quantitative electroencephalogram analysis during non-REM sleep in either primary or secondary RBD. The aim of this study was to assess the increase of SWS and to analyze different electroencephalographic frequency ranges during non-REM sleep in 28 idiopathic RBD patients compared with 28 age- and sex-matched healthy volunteers. Idiopathic RBD patients spent more time in SWS (men: 1.4%; women: 5.9%) than control subjects (men: 0.4%; women: 0.6%; p = 0.004). Spectral analyses demonstrated that idiopathic RBD patients had increased all-night delta power in comparison with control subjects (p = 002). This study shows an increase of SWS and power in the delta band during non-REM sleep in idiopathic RBD patients compared with control subjects. Results are discussed about the possible nigrostriatal dopaminergic impairment in RBD patients and the association between RBD and neurodegenerative disorders.