Delphine Oudiette

Rapid eye movement sleep disturbances in Huntington disease.

BACKGROUND Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). OBJECTIVE To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages and the length of CAG repeats. Because a mild hypocretin deficiency has been found in the brains of some patients with HD (hereinafter referred to as HD patients), we also tested the HD patients for narcolepsy. DESIGN AND PATIENTS Twenty-five HD patients (including 2 premanifest carriers) underwent clinical interview, nighttime video and sleep monitoring, and daytime multiple sleep latency tests. Their results were compared with those of patients with narcolepsy and control patients. RESULTS The HD patients had frequent insomnia, earlier sleep onset, lower sleep efficiency, increased stage 1 sleep, delayed and shortened rapid eye movement (REM) sleep, and increased periodic leg movements. Three HD patients (12%) had REM sleep behavior disorders. No sleep abnormality correlated with CAG repeat length. Reduced REM sleep duration (but not REM sleep behavior disorders) was present in premanifest carriers and patients with very mild HD and worsened with disease severity. In contrast to narcoleptic patients, HD patients had no cataplexy, hypnagogic hallucinations, or sleep paralysis. Four HD patients had abnormally low (< 8 minutes) daytime sleep latencies, but none had multiple sleep-onset REM periods. CONCLUSIONS The sleep phenotype of HD includes insomnia, advanced sleep phase, periodic leg movements, REM sleep behavior disorders, and reduced REM sleep but not narcolepsy. Reduced REM sleep may precede chorea. Mutant huntingtin may exert an effect on REM sleep and motor control during sleep.

Is obstructive sleep apnea a problem in Parkinson's disease?

BACKGROUND Parkinsons disease (PD) is associated with sleep disorders and daytime sleepiness. Upper airway dysfunction in PD may promote obstructive sleep apnea. However, the frequency and clinical relevance of sleep-disordered breathing in PD remains unclear. METHODS Sleep apnea symptoms, cardiovascular events and treatment were collected in 100 patients with PD (50 unselected, consecutive patients matched for age, sex and body mass index with 50 patients referred for sleepiness) and 50 in-hospital controls. The motor and cognitive status was evaluated in patients with PD. The 150 subjects underwent a video-polysomnography. RESULTS Sleep apnea (defined as an apnea-hypopnea index greater than 5) was less frequent in the PD group (27% patients, including 6% with mild, 11% with moderate and 10% with severe sleep apnea) than in the control group (40% in-hospital controls, p<0.002). Sleep apnea was not associated with increased sleepiness, nocturia, depression, cognitive impairment and cardiovascular events in patients with PD. Sleep apnea was more frequent and severe in the most disabled patients. Patients with PD did not display sleep hypoventilation, stridor and abnormal central sleep apnea. In patients with REM sleep behavior disorders, snoring and obstructive sleep apnea occurred during REM sleep, although the chin muscle tone was maintained. CONCLUSION Obstructive sleep apnea does not seem to be a clinically relevant issue in PD. Daytime sleepiness, nocturia and cognitive impairment are mostly caused by other, non-apneic mechanisms. The maintenance of chin muscle tone during REM sleep behavior disorder has no influence on the frequency of apneic events.

Upgrading the sleeping brain with targeted memory reactivation

A fundamental feature of human memory is the propensity for beneficial changes in information storage after initial encoding. Recent research findings favor the possibility that memory consolidation during sleep is instrumental for actively maintaining the storehouse of memories that individuals carry through their lives. The information that ultimately remains available for retrieval may tend to be that which is reactivated during sleep. A novel source of support for this idea comes from demonstrations that neurocognitive processing during sleep can benefit memory storage when memories are covertly cued via auditory or olfactory stimulation. Investigations of these subtle manipulations of memory processing during sleep can help elucidate the mechanisms of memory preservation in the human brain.

The Role of Memory Reactivation during Wakefulness and Sleep in Determining Which Memories Endure

Consolidation makes it possible for memories of our daily experiences to be stored in an enduring way. We propose that memory consolidation depends on the covert reactivation of previously learned material both during sleep and wakefulness. Here we tested whether the operation of covert memory reactivation influences the fundamental selectivity of memory storage—of all the events we experience each day, which will be retained and which forgotten? We systematically manipulated the value of information learned by 60 young subjects; they learned 72 object-location associations while hearing characteristic object sounds, and a number on each object indicated the reward value that could potentially be earned during a future memory test. Recall accuracy declined to a greater extent for low-value than for high-value associations after either a 90 min nap or a 90 min wake interval. Yet, via targeted memory reactivation of half of the low-value associations using the corresponding sounds, these memories were rescued from forgetting. Only cued associations were rescued when sounds were applied during wakefulness, whereas the entire set of low-value associations was rescued from forgetting when the manipulation occurred during sleep. The benefits accrued from presenting corresponding sounds show that covert reactivation is a major factor determining the selectivity of memory consolidation in these circumstances. By extension, covert reactivation may determine the ultimate fate of our memories, though wake and sleep reactivation might play distinct roles in this process, the former helping to strengthen individual, salient memories, and the latter strengthening, while also linking, categorically related memories together.

Abnormal sleep and sleepiness in Parkinson's disease.

Purpose of reviewSleep problems are frequent and disabling in patients with Parkinsons disease. Recent data provide major advances in the mechanisms and consequences of rapid eye movement sleep behavior disorders, insomnia and narcolepsy-like daytime sleepiness. Recent findingsA large series confirms that rapid eye movement sleep behavior disorders may precede parkinsonism or dementia (particuarly, but not exclusively, Lewy bodies dementia) for several years. In Parkinsons disease, rapid eye movement sleep behavior disorders expose patients to higher risks of dementia and hallucinations. Surprisingly, parkinsonism disappears during rapid eye movement sleep behavior disorders, suggesting basal ganglia are bypassed. The interest for structures controlling atonia during rapid eye movement sleep switches from the pedunculopontine nuclei to the locus subcoeruleus. The neuropathology of hypothalamus in Parkinsons disease indicates a massive hypocretin loss, probably underlying the narcolepsy phenotype. The benefit of the new, 24-h long acting ropinirole and transdermal rotigotine on sleep and sleepiness is modest. Eventually, the dopamine release in the mesocorticolimbic pathway is increased during rapid eye movement sleep, supporting its role in dopaminergic-induced vivid dreams. SummaryIn clinical practice, rapid eye movement sleep behavior disorders should be looked at as heralding neurodegenerative diseases in patients with mild cognitive impairment and as a risk factor for dementia and hallucinations in patients with Parkinsons disease.

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.

Do the eyes scan dream images during rapid eye movement sleep? Evidence from the rapid eye movement sleep behaviour disorder model

Rapid eye movements and complex visual dreams are salient features of human rapid eye movement sleep. However, it remains to be elucidated whether the eyes scan dream images, despite studies that have retrospectively compared the direction of rapid eye movements to the dream recall recorded after having awakened the sleeper. We used the model of rapid eye movement sleep behaviour disorder (when patients enact their dreams by persistence of muscle tone) to determine directly whether the eyes move in the same directions as the head and limbs. In 56 patients with rapid eye movement sleep behaviour disorder and 17 healthy matched controls, the eye movements were monitored by electrooculography in four (right, left, up and down) directions, calibrated with a target and synchronized with video and sleep monitoring. The rapid eye movement sleep behaviour disorder-associated behaviours occurred 2.1 times more frequently during rapid eye movement sleep with than without rapid eye movements, and more often during or after rapid eye movements than before. Rapid eye movement density, index and complexity were similar in patients with rapid eye movement sleep behaviour disorder and controls. When rapid eye movements accompanied goal-oriented motor behaviour during rapid eye movement sleep behaviour disorder (e.g. grabbing a fictive object, hand greetings, climbing a ladder), which happened in 19 sequences, 82% were directed towards the action of the patient (same plane and direction). When restricted to the determinant rapid eye movements, the concordance increased to 90%. Rapid eye movements were absent in 38-42% of behaviours. This directional coherence between limbs, head and eye movements during rapid eye movement sleep behaviour disorder suggests that, when present, rapid eye movements imitate the scanning of the dream scene. Since the rapid eye movements are similar in subjects with and without rapid eye movement sleep behaviour disorder, this concordance can be extended to normal rapid eye movement sleep.

The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy

Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinsons disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinsons disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinsons disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinsons disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system atrophy revealed more expressive faces, and movements that were faster and more ample in comparison with facial expression and movements during wakefulness. These movements were still somewhat jerky but lacked any visible parkinsonism. Cerebellar signs were not assessable. We conclude that parkinsonism also disappears during rapid eye movement sleep behaviour disorder in patients with multiple system atrophy, but this improvement is not due to enhanced dopamine transmission because these patients are not levodopa-sensitive. These data suggest that these movements are not influenced by extrapyramidal regions; however, the influence of abnormal cerebellar control remains unclear. The transient disappearance of parkinsonism here is all the more surprising since no treatment (even dopaminergic) provides a real benefit in this disabling disease.

A motor signature of REM sleep behavior disorder

The purpose of this study was to determine if there was a common pattern in movements during REM sleep behavior disorder (RBD).

Targeted Memory Reactivation during Sleep Depends on Prior Learning

STUDY OBJECTIVES When sounds associated with learning are presented again during slow-wave sleep, targeted memory reactivation (TMR) can produce improvements in subsequent location recall. Here we used TMR to investigate memory consolidation during an afternoon nap as a function of prior learning. PARTICIPANTS Twenty healthy individuals (8 male, 19-23 y old). MEASUREMENTS AND RESULTS Participants learned to associate each of 50 common objects with a unique screen location. When each object appeared, its characteristic sound was played. After electroencephalography (EEG) electrodes were applied, location recall was assessed for each object, followed by a 90-min interval for sleep. During EEG-verified slow-wave sleep, half of the sounds were quietly presented over white noise. Recall was assessed 3 h after initial learning. A beneficial effect of TMR was found in the form of higher recall accuracy for cued objects compared to uncued objects when pre-sleep accuracy was used as an explanatory variable. An analysis of individual differences revealed that this benefit was greater for participants with higher pre-sleep recall accuracy. In an analysis for individual objects, cueing benefits were apparent as long as initial recall was not highly accurate. Sleep physiology analyses revealed that the cueing benefit correlated with delta power and fast spindle density. CONCLUSIONS These findings substantiate the use of targeted memory reactivation (TMR) methods for manipulating consolidation during sleep. TMR can selectively strengthen memory storage for object-location associations learned prior to sleep, except for those near-perfectly memorized. Neural measures found in conjunction with TMR-induced strengthening provide additional evidence about mechanisms of sleep consolidation.