Movements and behaviors during spontaneous arousals in healthy young adults: an intermediary stage between wakefulness and sleep?

BACKGROUND: Arousals are common, sudden and transient elevations of the vigilance level during normal sleep, but arousal-associated behaviors have not yet been studied. OBJECTIVE: We aimed to describe the duration as well as motor and autonomic patterns associated with arousals across sleep stages in normal subjects. METHODS: The spontaneous arousals of 25 healthy young adults were randomly analyzed on polysomnography with body- and face-oriented video cameras. The duration of the heart rate response as well as the frequency, amplitude, speed, body segment and semiology of associated movements were measured. RESULTS: Among 624 arousals (258 in N2, 140 in N3 and 226 in REM sleep), REM sleep arousals had the shortest duration, and N3 arousals were associated with greater heart rate acceleration. Movements and behaviors (mostly involving the head and neck, then the upper limbs, with rare eyes opening and no turning in bed) were frequent during arousals (69.4% during N2 sleep, 89.3% during N3 and 93.8% during REM sleep). Arousals more frequently included ample, prolonged and whole-body movements during N3 sleep and fast movements and facial expressions during REM sleep. During N2 arousals, chewing was the most prevalent behavior. Some movements resembled orientation and comfort behaviors (flexing/rotating the neck and trunk, scratching, pulling the sheets, rubbing the nose, yawning, smiling, frowning and speaking), whereas others resembled sleep-associated automatisms (swallowing, chewing). CONCLUSION: In contrast with previous assumptions, most arousals are associated with movements. The type of movements suggests that arousal is an intermediary state between wakefulness and sleep.

Functional brain imaging using 18F-fluorodeoxyglucose positron emission tomography/computerized tomography in 138 patients with Kleine-Levin syndrome: an early marker?

Kleine-Levin syndrome is a rare disorder characterized by relapsing-remitting episodes of severe hypersomnia, cognitive impairment, apathy, derealization and behavioural disturbances. Between episodes, most patients experience normal sleep, mood and behaviour, but they may have some residual abnormalities in brain functional imaging; however, the frequency, localization and significance of abnormal imaging are unknown, as brain functional imaging have been scarce and heterogenous [including scintigraphy 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (FDG-PET/CT) and functional MRI during resting state and cognitive effort] and based on case reports or on group analysis in small groups. Using visual individual analysis of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography at the time of Kleine-Levin syndrome diagnosis, we examined the frequency, localization and clinical determinants of hypo- and hypermetabolism in a cross-sectional study. Among 179 patients with Kleine-Levin syndrome who underwent 18F-fluorodeoxyglucose positron emission tomography/computerized tomography, the visual analysis was restricted to the 138 untreated patients studied during asymptomatic periods. As many as 70% of patients had hypometabolism, mostly affecting the posterior associative cortex and the hippocampus. Hypometabolism was associated with younger age, recent (<3 years) disease course and a higher number of episodes during the preceding year. The hypometabolism was more extensive (from the left temporo-occipital junction to the entire homolateral and then the bilateral posterior associative cortex) at the beginning of the disorder. In contrast, there was hypermetabolism in the prefrontal dorsolateral cortex in half of the patients (almost all having concomitant hypometabolism in the posterior areas), which was also associated with younger age and shorter disease course. The cognitive performances (including episodic memory) were similar in patients with versus without hippocampus hypometabolism. In conclusion, hypometabolism is frequently observed upon individual visual analysis of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography during asymptomatic Kleine-Levin syndrome periods; it is mostly affecting the posterior associative cortex and the hippocampus and is mostly in young patients with recent-onset disease. Hypometabolism provides a trait marker during the first years of Kleine-Levin syndrome, which could help clinicians during the diagnosis process.

Emerging psychiatric disorders in Kleine-Levin syndrome.

In Kleine-Levin syndrome (KLS), episodes of hypersomnia and cognitive, psychiatric and behavioural disturbances alternate with asymptomatic periods in adolescents. We evaluated whether psychiatric disorders would emerge during asymptomatic periods in a naturalistic, uncontrolled clinical cohort. Patients with primary KLS underwent psychiatric interviews at diagnosis and every year for 1-10 years, leading to diagnosis of former and present comorbid psychiatric disorders. Among the 115 patients (65.2% male and aged 16.1 ± 4.8 years at KLS onset), 19 (16.5%) had a history of psychiatric disorder prior to KLS onset, which persisted afterwards in 10. Twenty-five (21%) patients developed a new, comorbid psychiatric disorder 1-6 years after KLS onset, during 'asymptomatic' periods, including mood disorders (n = 14; including major depressive episodes, n = 8; recurrent depressive episodes, n = 2; bipolar I disorder, n = 1; dysthymic disorder, n = 1; adjustment disorder with depressive mood, n = 1; and mood disorder not otherwise specified, n = 1), anxiety disorders (n = 7), eating disorders (n = 2), psychotic disorders not otherwise specified (n = 2), schizoaffective disorder (n = 1) and cannabis dependence (n = 1). Six patients attempted suicide: two before and two after KLS onset, and two during episodes. Female sex, longer disease course, longer time incapacitated (356 ± 223 versus 155 ± 186 days) and more frequent psychiatric symptoms during episodes (but no family or personal history of psychiatric disorders) were associated with emerging psychiatric disorders. Contrary to the alleged benignity of KLS and normality between episodes, one KLS patient in five suffers from emerging psychiatric disorders. These disorders may depend on personal vulnerability and, most probably, on psychiatric symptoms during episodes.

IV steroids during long episodes of Kleine-Levin syndrome.

OBJECTIVE: To retrospectively compare the benefits (episode cessation) and risks of IV methylprednisolone (IV-MP) vs abstention during prolonged Kleine-Levin syndrome (KLS) episodes. METHODS: A total of 26 patients with KLS received 1 g/d IV-MP for 3 days during 1 to 6 episodes each (totaling 43 IV-MP sessions). The change of episode duration with IV-MP (vs previous episode duration) was compared with the change duration between 2 consecutive episodes in 48 untreated patients matched for age, sex, age at KLS onset, number of episodes, and disease duration (more treated than untreated patients had long episodes). RESULTS: Eleven patients (42.3%) had an episode that was at least 1 week shorter than the preceding one when they received IV-MP therapy, whereas shorter episodes were significantly less frequent (10.4%) in the untreated group. This benefit was more marked (65.5% responders, 12 fewer days in an episode vs 0 days in the untreated patients) when IV-MP was infused before the 10th day of the episode. Mild, transient adverse effects (insomnia, muscle pain, nervousness/restlessness, but no manic switching) were reported by 61.3% of patients. No specific responder profile was identified. CONCLUSION: In this open-labeled, naturalistic study, early IV-MP (following the protocol for multiple sclerosis relapses) had a good benefit/risk ratio during KLS episodes in patients with long episodes (with half of the patients having an early cessation of episodes). CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with long episodes of KLS, IV steroids decrease the duration of KLS episodes.

Predictors of long-term effectiveness to mandibular repositioning device treatment in obstructive sleep apnea patients after 1000 days.

OBJECTIVE/BACKGROUND: In obstructive sleep apnea (OSA), long-term adherence to treatment is crucial. This prospective single-center study investigated factors associated with long-term adherence to mandibular repositioning device (MRD) therapy. PATIENTS/METHODS: All OSA patients who had MRD treatment initiated in the previous year were prospectively contacted to evaluate long-term effectiveness and compliance. Long-term adherence was based on continuation of treatment (yes/no). Predictors of long-term adherence were analyzed using an adjusted multivariate analysis. RESULTS: Median follow-up was 1002 days (interquartile range: 668-1345) in 279 patients (age 58 [50-64] years); 63% of patients were continuing MRD treatment with a good efficacy, tolerability and compliance over time. In some patients, relapse of nocturia was observed while efficacy was maintained for snoring and somnolence. In adjusted multivariate analysis, significant predictors of continuing MRD treatment were early ≥50% reduction in AHI (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.466-5.10; p = 0.0002) and complete symptom resolution (OR 3.83, 95% CI 1.74-8.48; p = 0.0014). In the 37% of patients who stopped MRD treatment, median treatment duration was 351 (174-752) days. The main reasons for late stopping of treatment were inefficacy (26.2%), discomfort (25.2%) and side effects (21.4%). CONCLUSIONS: After three years, MRD was effective for the two-thirds of OSA patients who continued treatment. Relapse of nocturia might be an early signal of MRD wear that may explain long-term cessation of treatment in some patients. Short-term control of OSA by MAD was predictive of long-term efficiency. The major criteria were a ≥50% reduction in AHI and complete symptom resolution at short-term evaluation.

Long-Term Cognitive Impairment in Kleine-Levin Syndrome.

STUDY OBJECTIVES: In Kleine-Levin syndrome (KLS), episodes of hypersomnia, cognitive, and behavioral disturbances alternate with asymptomatic periods. Because 50% of patients report decreased academic performances, we evaluated their cognitive status during asymptomatic periods, determinants of deficits, and changes during follow-up. METHODS: The cognitive assessment during asymptomatic periods in all consecutive patients with typical KLS and healthy controls included the non-verbal intelligence quotient (Raven Progressive Matrices), the Trail Making Test, the Stroop Color-Word Test, the Wechsler Memory Test, verbal fluencies, the Free and Cued Learning Memory Test, and the Rey-Osterreith Complex Figure. Cognitive status was reevaluated after 0.5 to 2 y in 44 patients. RESULTS: At baseline, compared with the 42 controls, the 122 patients with KLS exhibited lower non-verbal intelligence quotient, speed of processing, attention, and reduced retrieval strategies in episodic memory. Higher episode frequency, shorter episode duration, shorter time since last episode, deeper sleep, and megaphagia during episodes predicted impaired memory. The visuoconstructional abilities and non-verbal memory were intact. After a mean follow-up of 1.7 ± 1.0 y, the episode frequency decreased from 4.6 ± 4.8 to 1.7 ± 1.9/y. The logical reasoning and attention improved, the processing speed remained low, and the retrieval strategies in verbal memory further worsened. CONCLUSIONS: In this field study, one-third of patients with KLS have long-term cognitive deficits affecting retrieval and processing speed. Cognitive function should be systematically tested in patients with KLS, which appears important to help patients in their academic studies.

Evidence that non-dreamers do dream: a REM sleep behaviour disorder model.

To determine whether non-dreamers do not produce dreams or do not recall them, subjects were identified with no dream recall with dreamlike behaviours during rapid eye movement sleep behaviour disorder, which is typically characterised by dream-enacting behaviours congruent with sleep mentation. All consecutive patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye movement sleep behaviour disorder associated with Parkinson's disease who underwent a video-polysomnography were interviewed regarding the presence or absence of dream recall, retrospectively or upon spontaneous arousals. The patients with no dream recall for at least 10 years, and never-ever recallers were compared with dream recallers with rapid eye movement sleep behaviour disorder regarding their clinical, cognitive and sleep features. Of the 289 patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients had no dream recall, including four (1.4%) patients who had never ever recalled dreams, and four patients who had no dream recall for 10-56 years. All non-recallers exhibited, daily or almost nightly, several complex, scenic and dreamlike behaviours and speeches, which were also observed during rapid eye movement sleep on video-polysomnography (arguing, fighting and speaking). They did not recall a dream following sudden awakenings from rapid eye movement sleep. These eight non-recallers with rapid eye movement sleep behaviour disorder did not differ in terms of cognition, clinical, treatment or sleep measures from the 17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex and disease. The scenic dreamlike behaviours reported and observed during rapid eye movement sleep in the rare non-recallers with rapid eye movement sleep behaviour disorder (even in the never-ever recallers) provide strong evidence that non-recallers produce dreams, but do not recall them. Rapid eye movement sleep behaviour disorder provides a new model to evaluate cognitive processing during dreaming and subsequent recall.