A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder.

BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) is characterized by prominent dream-enacting behaviors, often resulting in sleep-related injuries. OBJECTIVES: This study aimed to prospectively examine the treatment response of people with RBD treated with clonazepam, by quantitatively delineating the characteristic changes in the clinical and polysomnographic features, and to explore the factors associated with this response. METHODS: Patients diagnosed with idiopathic RBD (iRBD) were consecutively recruited and invited to complete clinical and polysomnographic (PSG) assessments and self-administered questionnaires (including the modified REM Sleep Behavior Questionnaire, RBDQ-3M) before and after the initiation of treatment with clonazepam. RESULTS: Thirty-nine iRBD patients (male: 74.4%, mean age at diagnosis: 68.3 ± 7.8 years) were recruited with a follow-up duration of 28.8 ± 13.3 months. Clonazepam was offered as the first-line treatment (starting dose: 0.43 ± 0.16 mg, range: 0.125-1.00; dose at follow-up: 0.98 ± 0.63 mg, range: 0.125-3). Treatment response, as defined by a complete elimination of sleep-related injuries and potentially injurious behaviors to self and/or to bed partner, at follow-up was reported in 66.7% of the overall study subjects. Frequency of disturbing dreams with violent and frightening content and vigorous behavioral RBD symptoms was significantly reduced, while residual nocturnal symptoms and an increase in REM-related EMG activities were observed at follow-up. Less optimal treatment outcomes were found to be associated with the presence of comorbid obstructive sleep apnea and earlier onset of RBD. CONCLUSIONS: Clonazepam differentially changes dream affect and content, as well as reduces vigorous verbal and motor behaviors. Residual RBD symptoms are common, despite treatment. Other more effective alternative or adjunctive interventions are needed for better clinical management of RBD.

Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy.

OBJECTIVES: To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. METHODS: To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. RESULTS: The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7-149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. CONCLUSION: Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis.

Does rapid eye movement sleep behavior disorder exist in psychiatric populations? A clinical and polysomnographic case-control study.

OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) has been increasingly reported in patients with psychiatric disorders (pRBD). Although a close association with the usage of psychotropics has been postulated, it remains elusive whether psychotropics are the only causative factor of RBD symptoms in psychiatric populations. Moreover, there is limited literature documenting and quantifying the clinical and polysomnographic features in this population. METHODS: A case-control study comparing the clinical and polysomnographic features of 31 pRBD patients with: (1) Age-, sex-, and psychiatric diagnoses-matched controls; and (2) Typical idiopathic RBD (tRBD) patients. RESULTS: Despite being prescribed with similar psychotropics, pRBD patients had more dream-enacting behaviors (p<0.01), sleep-related injuries (p<0.01), and nightmares (p<0.01) than the psychiatric controls. pRBD patients were younger with more females, but they had comparable sleep-related injuries to tRBD. Both tRBD and pRBD had more REM-related muscle activity than controls (p<0.01) and the effect remained significant after adjusting for age, gender, and use of antidepressants. CONCLUSIONS: Our study suggests that pRBD had comparable clinical features and consequences to those of tRBD. The occurrence of RBD symptoms in these patients may be related to a constellation of factors, including individual predisposition, depressive illness, antidepressants, and other clinical factors. Given the association of RBD and neurodegeneration in tRBD, further prospective follow-up of these patients is warranted.

Amelioration of obstructive sleep apnea in REM sleep behavior disorder: implications for the neuromuscular control of OSA.

OBJECTIVES: The relationship between REM sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) remains unclear. We aimed to (1) explore the association of REM-related EMG activity (REMREEA) with OSA in RBD patients; (2) compare the severity of OSA between RBD patients with OSA (RBD-OSA) and their age-, sex-, AHI-, and BMI- matched OSA controls. DESIGN: a. Correlation study in consecutive RBD subjects and b. case-control study SETTING: Sleep laboratory PARTICIPANTS: 71 RBD patients in the correlation study and 55 subjects (28 RBD-OSA cases and 27 OSA controls) in the case-control study. INTERVENTION: N/A METHODS: Polysomnographic assessment to document the sleep architecture, sleep apnea related parameters, and REMREEA. RESULTS: (1) In the correlation study, increased REMREEA was associated with lower severity of OSA in RBD patients, including total AHI (r = -0.263), NREM AHI (r = -0.242), obstructive AHI (r = -0.265), and mean apnea duration (r = -0.353) (P < 0.05). (2) In the case-control study, RBD-OSA patients had lesser severity of sleep apnea parameters than OSA controls in terms of higher nadir SpO(2) (85.7% ± 4.9% vs 80.8% ± 5.9%, P < 0.01), shorter maximum hypopnea duration (53.8 ± 16.7 vs 69.4 ± 22.4 seconds, P < 0.05), and maximum (45.8 ± 20.5 vs 60.8 ± 19.6 sec, P < 0.01) and mean apnea duration (22.3 ± 8.1 vs 26.3 ± 5.8 sec, P < 0.05). Significant interaction effects indicated that the usual REM sleep exacerbation of sleep apneas was seen only in OSA controls but not in RBD subjects. CONCLUSIONS: This study demonstrated that excessive EMG activity in RBD might protect patients against severe OSA and suggests this may be a naturalistic model for understanding neuromuscular control of OSA.