J. Montplaisir

Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder

Objective: Idiopathic REM sleep behavior disorder (RBD) is a potential preclinical marker for the development of neurodegenerative diseases, particularly Parkinson disease (PD) and Lewy body dementia. However, the long-term risk of developing neurodegeneration in patients with idiopathic RBD has not been established. Obtaining an accurate picture of this risk is essential for counseling patients and for development of potential neuroprotective therapies. Methods: We conducted a follow-up study of all patients seen at the sleep disorders laboratory at the Hôpital du Sacré Coeur with a diagnosis of idiopathic RBD. Diagnoses of parkinsonism and dementia were defined according to standard criteria. Survival curves were constructed to estimate the 5-, 10-, and 12-year risk of developing neurodegenerative disease. Results: Of 113 patients, 93 (82%) met inclusion criteria. The mean age of participants was 65.4 years and 75 patients (80.4%) were men. Over the follow-up period, 26/93 patients developed a neurodegenerative disorder. A total of 14 patients developed PD, 7 developed Lewy body dementia, 4 developed dementia that met clinical criteria for AD, and 1 developed multiple system atrophy. The estimated 5-year risk of neurodegenerative disease was 17.7%, the 10-year risk was 40.6%, and the 12-year risk was 52.4%. Conclusions: Although we have found a slightly lower risk than other reports, the risk of developing neurodegenerative disease in idiopathic REM sleep behavior disorder is substantial, with the majority of patients developing Parkinson disease and Lewy body dementia.

REM sleep behavior disorder and REM sleep without atonia in Parkinson’s disease

Objective To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. Background The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. Methods Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. Results One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%;p = 0.003). ConclusionsRBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.

Sleep Bruxism: Validity of Clinical Research Diagnostic Criteria in a Controlled Polysomnographic Study

The clinical validity of diagnostic criteria for sleep orofacial motor activity-more specifically, bruxism-has never been tested. Polysomnographic recordings from 18 bruxers and 18 asymptomatic subjects, selected according to American Sleep Disorders Association criteria, were analyzed (1) to discriminate sleep bruxism from other orofacial motor activities and (2) to calculate sensitivity, specificity, and predictive values of research criteria. Clinical observations and reports revealed that all 18 bruxers reported frequent tooth-grinding during sleep. Tooth wear was noted in 16 out of 18 bruxers and jaw discomfort reported by six of them. These findings were present in none of the controls. The analysis of polysomnographic data showed that the asymptomatic subjects presented a mean of 1.7 ± 0.3 bruxism episodes per hour of sleep (sustained or repetitive bursting activity in jaw closer muscles), while bruxers had a significantly higher level of activity: 5.4 ± 0.6. Controls exhibited 4.6 ± 0.3 bruxism bursts per episode and 6.2 (from 0 to 23) bruxism bursts per hour of sleep, whereas bruxers showed, respectively, 7.0 ± 0.7 and 36.1 (5.8 to 108). Bruxism-like episodes with at least two grinding sounds were noted in 14 of the 18 bruxers and in one control. The two groups exhibited no difference in any of the sleep parameters. Based on the present findings, the following polysomnographic diagnostic cut-off criteria are suggested: (1) more than 4 bruxism episodes per hour, (2) more than 6 bruxism bursts per episode and/or 25 bruxism bursts per hour of sleep, and (3) at least 2 episodes with grinding sounds. When the polysomnographic bruxism-related variables were combined under logistic regression, the clinical diagnosis was correctly predicted in 81.3% of the controls and 83.3% of the bruxers. The validity of these clinical research criteria needs now to be challenged in a larger population, over time, and in subjects presenting various levels of severity of sleep bruxism.

Development of sleep patterns in early adolescence

This study examines the developmental changes of sleep patterns as a function of gender and puberty and assesses the prevalence of sleep habits and sleep disturbances in early adolescence. It also investigates the relationship between sleep patterns, sleep habits and difficulty falling asleep and nocturnal awakenings. The present analyses are based on results available for 588 boys and 558 girls for whom mothers completed questions concerning demographics and sleep at annual intervals when their child was aged 10–13 years. The results indicated that nocturnal sleep times decreased, bedtimes were delayed and differences between weekend and school day sleep schedules progressively increased with age. Gender and puberty were both associated with the timing of sleep on weekends. Girls presented longer weekend time in bed (TIB) and later weekend wake time than boys. Similarly, subjects with higher pubertal status showed longer weekend TIB and later weekend wake time than subjects with lower pubertal status. Difficulty falling asleep was associated with later weekend wake time and with sleeping with a night light. In conclusion, the gender differences commonly reported in adolescents’ sleep patterns are most likely explained by girls’ higher pubertal status. This study emphasizes the link between puberty and a putative physiological need for more sleep, in presence of a general reduction of sleep times during adolescence. From age 10–13 years, the delay and lengthening of the sleep period on weekends in comparison to schooldays is associated with difficulty falling asleep.

REM SLEEP BEHAVIOR DISORDER PREDICTS COGNITIVE IMPAIRMENT IN PARKINSON DISEASE WITHOUT DEMENTIA

Objective: To assess the relationship between the presence of REM sleep behavior disorder (RBD) and the cognitive profile of nondemented patients with Parkinson disease (PD). Background: Cognitive impairment is an important nonmotor symptom in PD. Waking EEG slowing in nondemented PD has been related to the presence of RBD, a parasomnia affecting brainstem structures and frequently reported in PD. For this reason, RBD may be associated with cognitive impairment in PD. Methods: Thirty-four patients with PD (18 patients with polysomnographic-confirmed RBD and 16 patients without RBD) and 25 healthy control subjects matched for age and educational level underwent sleep laboratory recordings and a comprehensive neuropsychological assessment. Results: Patients with PD and concomitant RBD showed significantly poorer performance on standardized tests measuring episodic verbal memory, executive functions, as well as visuospatial and visuoperceptual processing compared to both patients with PD without RBD and control subjects. Patients with PD without RBD had no detectable cognitive impairment compared to controls. Conclusions: This study shows that cognitive impairment in nondemented patients with Parkinson disease (PD) is closely related to the presence of REM sleep behavior disorder, a sleep disturbance that was not controlled for in previous studies assessing cognitive deficits in PD. GLOSSARY: BDI-II = Beck-II Depression Inventory; DLB = dementia with Lewy bodies; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; EOG = electro-oculograms; ICSD = International Classification of Sleep Disorders; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PD-NRBD = patients with PD without RBD; PD-RBD = patients with concomitant RBD; RAVLT = Rey Auditory Verbal Learning Test; RBD = REM sleep behavior disorder; UPDRS = Unified Parkinsons Disease Rating Scale.

Periodic leg movements in REM sleep behavior disorder and related autonomic and EEG activation

Objective: To assess the frequency of periodic leg movements (PLM) in idiopathic REM sleep behavior disorder (RBD) and to analyze their polysomnographic characteristics and associated autonomic and cortical activation. Background: PLM during sleep (PLMS) and wakefulness (PLMW) are typical features of restless legs syndrome (RLS), but are also frequently observed in patients with RBD. Methods: Forty patients with idiopathic RBD underwent one night of polysomnographic recording to assess PLMS frequency. PLM features, PLMS-related cardiac activation during stage 2 sleep, and EEG changes were analyzed in 15 of these patients with RBD. Results were compared with similar data obtained in 15 sex- and age-matched patients with primary RLS. Results: Twenty-eight (70%) of 40 patients with RBD showed a PLMS index greater than 10. No between-group differences were found in sleep architecture or indexes of PLMW and PLMS during non-REM sleep, but a trend for a higher PLMS index during REM sleep was found in patients with RBD. PLM mean duration and interval in the two conditions were similar. A transient tachycardia followed by a bradycardia was observed in close association with every PLMS in both groups, but the amplitude of the cardiac activation was significantly reduced in patients with RBD. In addition, significantly fewer PLMS were associated with microarousal in this condition. Conclusions: Periodic leg movements are very common in idiopathic RBD, occurring in all stages of sleep, especially during REM sleep. In idiopathic RBD, the reduction of cardiac and EEG activation associated with PLMS suggests the presence of an impaired autonomic and cortical reactivity to internal stimuli.

The effects of pramipexole in REM sleep behavior disorder

The authors evaluated the effects of pramipexole, a dopaminergic D2-D3 receptor agonist, on eight patients with idiopathic REM sleep behavior disorder. Five patients reported a sustained reduction in the frequency or intensity of sleep motor behaviors, which was confirmed by video recording, although no change was observed for the percentage of phasic EMG activity during REM sleep. Surprisingly, a decrease in the percentage of time spent with REM sleep muscle atonia was observed with treatment. The treatment did not modify the indexes of periodic leg movements.

Rhythmic Masticatory Muscle Activity during Sleep in Humans

Rhythmic Masticatory Muscle Activity (RMMA) is frequently observed during sleep in normal subjects and sleep bruxers. We hypothesized that some normal subjects exhibit RMMA at a lower frequency than sleep bruxers. Polysomnographic data from 82 normal subjects were compared with data from 33 sleep bruxers. RMMA episodes were defined as three or more consecutive bursts of masseter EMG activity, with or without tooth-grinding. Such episodes were observed in nearly 60% of normal subjects. A lower frequency of episodes was noted in normal subjects than in bruxers. Sleep organization was similar between groups. Bruxers had twice as many masseter muscle bursts per episode and episodes of higher amplitude compared with controls with RMMA. The high prevalence of RMMA observed in normal subjects suggests that this activity is related to certain sleep-related physiological functions, including autonomic activation.

Identification of a Sleep Bruxism Subgroup with a Higher Risk of Pain

Sleep bruxism research diagnostic criteria (SB-RDC) have been applied since 1996. This study was performed to validate these criteria and to challenge the hypothesis that pain is associated with lower frequencies of orofacial activities. Polygraphic recordings were made of 100 individuals presenting with a clinical diagnosis of sleep bruxism and 43 control individuals. TwoStep Cluster analyses (SPSS) were performed with sleep bruxism variables to reveal groupings among sleep bruxers and control individuals. Participants completed questionnaires during screening, diagnosis, and recording sessions. Cluster analysis identified three subgroups of sleep bruxers. Interestingly, 45 of the 46 sleep bruxers with values below SB-RDC were classified in the low-frequency cluster. These individuals were more likely to complain of pain and fatigue of masticatory muscles than were the higher-frequency sleep bruxers (odds ratios > 3.9, p < 0.01). Sleep bruxers were distributed among three heterogeneous groups. Sleep bruxers with low frequencies of orofacial activities were more at risk of reporting pain.

Evidence that Experimentally Induced Sleep Bruxism is a Consequence of Transient Arousal

Spontaneous rhythmic masticatory muscle activity (RMMA) during sleep occurs more frequently following spontaneous transient micro-arousal in patients with sleep bruxism (SB) and normal controls. Here, we tested the hypothesis that an experimental arousal would be followed by an increase in RMMA. We identified RMMA on polygraphic recordings taken before and after sensory stimulation to induce experimental arousal in eight SB patients and eight matched normal subjects. The rate of experimental arousal and the level of resting electromyographic activity in masseter and suprahyoid muscles during sleep did not differ between the groups. In both, muscle tone and heart rate increased during the experimental arousal. Although post-arousal RMMA occurred in all SB patients, it was seen in only one normal subject. Moreover, tooth-grinding occurred during 71% of the evoked RMMA in SB patients. These results support the hypothesis that SB is an exaggerated form of oromotor activity associated with sleep micro-arousal.