Donepezil‐induced sleep spindle in a patient with dementia with Lewy bodies: a case report

Here, we report a case of rapid eye movement sleep behavioural disorder in an elderly patient with dementia with Lewy bodies. Pretreatment polysomnography revealed atonia during rapid eye movement sleep, absence of sleep spindles and loss of slow‐wave sleep. Administration of donepezil, an acetylcholinesterase inhibitor, markedly improved delusional symptoms and cognitive function. Pretreatment polysomnography performed after donepezil administration revealed a considerable number of sleep spindles. The effects of cholinergic modulation induced by donepezil seemed to cause remarkable improvement in mental status, incorporating associated with sleep spindles generated by the thalamocortical circuit involved in this patient.     

Absence of rapid eye movement sleep behavior disorder in 11 members of the pallidopontonigral degeneration kindred

BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) is a parasomnia that is manifested by dream enactment behavior. The electrophysiologic substrate for RBD on polysomnography is rapid eye movement sleep without atonia. Rapid eye movement sleep behavior disorder likely stems from neuronal network dysfunction in the brainstem, although it is not yet clear which specific networks are involved. Rapid eye movement sleep behavior disorder is often associated with the sporadic synucleinopathies but rarely associated with the sporadic tauopathies. There are no reports on the possible association of rapid eye movement sleep without atonia and RBD with any familial tauopathy. OBJECTIVE: To characterize the clinical sleep and polysomnography features in a kindred with a familial tauopathy. METHODS: We performed standard polysomnography in 11 members of the pallidopontonigral degeneration kindred irrespective of any sleep-related complaints. Neuropathologic findings were analyzed in those who subsequently underwent autopsy. RESULTS: Six affected and 5 genealogically at-risk family members were studied. None of the 11 had a history of dream enactment behavior. Nine of the 11 members attained sufficient rapid eye movement sleep on polysomnography, and the electrophysiologic features of rapid eye movement sleep without atonia and behavioral manifestations of RBD were absent in all subjects. Neuropathologic examination of 4 affected individuals revealed marked nigral degeneration in 3 along with mild degenerative changes in the locus coeruleus, pontine nuclei and tegmentum, and medullary tegmentum. CONCLUSIONS: These findings argue against nigral degeneration being the primary cause of RBD. The absence of the historical, electrophysiologic, and behavioral manifestations of RBD in this kindred provides further evidence that RBD is rare in the sporadic and familial tauopathies. The difference in frequencies of RBD associated with the synucleinopathies compared with the tauopathies suggests differences in the selective vulnerability of brainstem circuits between the synucleinopathies and tauopathies.     

Polysomnographic study of sleeplessness and oneiricisms in the alcohol withdrawal syndrome

We describe a polysomnographic observation of the acute phase of the alcohol withdrawal syndrome, characterized by an alteration of the sleep-wake cycle and by the absence of non-rapid eye movement sleep. An atypical transitional state between rapid eye movement sleep and wake with hallucinations and enacting-dream behaviors represented the sole sleep pattern. Analogies of alcohol withdrawal syndrome with fatal familial insomnia and Morvan's fibrillary chorea suggest a common pathophysiological mechanism in these conditions.     

Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies

The purpose of this study was to determine whether dementia with Lewy bodies with and without probable rapid eye movement sleep behavior disorder differ clinically or pathologically. Patients with dementia with Lewy bodies (DLB) with probable rapid eye movement sleep behavior sleep disorder (n = 71) were compared with those without it (n = 19) on demographics, clinical variables (core features of dementia with Lewy bodies, dementia duration, rate of cognitive/motor changes), and pathologic indices (Lewy body distribution, neuritic plaque score, Braak neurofibrillary tangle stage). Individuals with probable rapid eye movement sleep behavior disorder were predominantly male (82% vs 47%) and had a shorter duration of dementia (mean, 8 vs 10 years), earlier onset of parkinsonism (mean, 2 vs 5 years), and earlier onset of visual hallucinations (mean, 3 vs 6 years). These patients also had a lower Braak neurofibrillary tangle stage (stage IV vs stage VI) and lower neuritic plaque scores (18% vs 85% frequency), but no difference in Lewy body distribution. When probable rapid eye movement sleep behavior disorder developed early (at or before dementia onset), the onset of parkinsonism and hallucinations was earlier and Braak neurofibrillary tangle stage was lower compared with those who developed the sleep disorder after dementia onset. Women with autopsy-confirmed DLB without a history of dream enactment behavior during sleep had a later onset of hallucinations and parkinsonism and a higher Braak NFT stage. Probable rapid eye movement sleep behavior disorder is associated with distinct clinical and pathologic characteristics of dementia with Lewy bodies.     

Neuropathology of sleep disorders: a review

Sleep disorders are important manifestations of neurodegenerativediseases and sometimes are clinically evident well before the onset of other neurological manifestations. This review addresses theneuroanatomical basis and the mechanisms of sleep regulation in humans in relation to the neuropathology of entities associated with sleep disturbances in selected diseases, including Alzheimer disease, progressive supranuclear palsy, Lewy body disorders, multiple-system atrophy, and fatal familial insomnia. This includes abnormalities of circadian rhythm, insomnia, narcolepsy, rapid eye movements sleep behavior disorders, and excessive daytime sleepiness.     

Sleep and Suicide in Psychiatric Patients

Suicidal patients often report problems with their sleep. Although sleep-related complaints and EEG (electroencephalographic) changes have been seen widely across the spectrum of psychiatric disorders, sleep complaints such as insomnia, hypersomnia, nightmares, and sleep panic attacks are more common in suicidal patients. The subjective quality of sleep as measured by self-rated questionnaires also appears to be more disturbed in suicidal depressive patients. Sleep studies have reported various polysomnographic findings including increased REM (rapid eye movement) time and REM activity in suicidal patients with depression, schizoaffective disorder, and schizophrenia. One mechanism responsible for this possible association between suicide and sleep could be the role of serotonin (5HT). Serotonergic function has been found to be low in patients who attempted and/or completed suicide, particularly those who used violent methods. Aggression dyscontrol appears to be an intervening factor between serotonin and suicide. Additionally, agents that enhance serotonergic transmission decrease suicidal behavior. Serotonin has also been documented to play an important role in onset and maintenance of slow wave sleep and in REM sleep. CSF 5-HIAA levels have been correlated with slow wave sleep in patients with depression as well as schizophrenia. Moreover, 5HT2 receptor antagonists have improved slow wave sleep. Further studies are needed to investigate the possible role of sleep disturbance in suicidal behavior.     

Visual declarative memory is associated with non-rapid eye movement sleep and sleep cycles in patients with chronic non-restorative sleep

OBJECTIVE: Sleep contributes to processes of memory, but many questions still remain open. The aim of this study was to test the role of different aspects of sleep for memory performance in a group of patients with chronic non-restorative sleep. METHODS: Forty-two consecutive patients (mean age 40.3 years; 31 women) with non-restorative sleep were included. All subjects underwent polysomnography for diagnostic reasons and obtained the following diagnoses (International Classification of Sleep Disorders, ICSD): psychophysiological or idiopathic insomnia (N=18), paradoxical insomnia (N=13), mild hypersomnia (N=6), and dysthymic disorder (N=5). Patients with sleep-related breathing disorders or restless legs were not included. Prior to polysomnography on the second night and the next morning, neuropsychological tests were performed. Declarative memory was tested by the Rey-Osterrieth Complex Figure Test and a paired associative word list. Procedural learning was assessed by a mirror-tracing skill. RESULTS: Visual declarative memory performance was significantly associated with total sleep time, sleep efficiency, duration of non-rapid eye movement (NREM) sleep and number of NREM-REM sleep cycles, but not with specific measures of REM sleep or slow wave sleep. CONCLUSIONS: Further indications of a role of sleep, and in particular of NREM sleep and sleep organization, for visual declarative memory were found.     

Positron emission tomography studies of sleep and sleep disorders

Using positron emission tomography (PET) it is possible to perform an in vivo study of cerebral physiological and biochemical processes in man. Employing this technique in sleep studies, decreased cerebral metabolic rates for glucose during slow wave sleep compared with those seen during wakefulness were first demonstrated, whereas similar rates of cerebral glucose metabolism were observed during paradoxical sleep and wakefulness. More recently, regional modifications of cerebral blood flow during sleep have also been demonstrated. During slow wave sleep, cerebral blood flow is decreased particularly in the prefrontal cortex. Rapid eye movement sleep is characterized by activation of the pons, thalami, amygdaloid complexes and a number of cortical areas (e.g. the anterior cingulate cortex). Although data remain incomplete, a variety of sleep disorders, including narcolepsy, fatal familial insomnia and continuous spike-and-wave discharges during slow sleep have been investigated. These results are briefly reviewed.

     

Stages 1–2 non–rapid eye movement sleep behavior disorder associated with dementia: A new parasomnia?

A 55-year-old woman with a progressive dementia and frontal syndrome was hospitalized because she was agitated every night after falling asleep (spoke, laughed, cried, tapped, kicked, walked, and fell down). She slept 5.5 hours during video polysomnography, but the theta rhythm electroencephalograph recording typical of sleep stages 1 to 2 and the spindles and K-complexes typical of sleep stage 2 contrasted with continuous muscular twitching, prominent rapid eye movements, vocalizations, and continuous, complex, purposeful movements typical of rapid eye movement (REM) sleep behavior disorder. This newly described stages 1--2 non-REM sleep behavior disorder suggests that central motor pattern generators were disinhibited during non-REM sleep.     

Abnormal sleep and sleepiness in Parkinson's disease

PURPOSE OF REVIEW: Sleep problems are frequent and disabling in patients with Parkinson's 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 FINDINGS: A 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 Parkinson's 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 Parkinson's 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. SUMMARY: In 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 Parkinson's disease.     

Sleep in schizophrenia: impairments, correlates, and treatment.

In untreated schizophrenia, psychotic decompensation is associated with profound insomnia, one of the prodromal symptoms associated with psychotic relapse. First- and second-generation antipsychotic medication can ameliorate this insomnia, but side effects may include sedation or residual insomnia. Patients who are clinically stable and medicated may continue to experience disturbed sleep, including long sleep-onset latencies, poor sleep efficiency, slow wave sleep deficits, and short rapid eye movement latencies. Schizophrenia also can be associated with comorbid sleep disorders, which may be enhanced or induced by antipsychotic medication. Sleep disorders in schizophrenia should be treated vigorously because normalized sleep and its restorative processes may be essential for a positive clinical outcome.     

Sleep and youth suicidal behavior: a neglected field

PURPOSE OF REVIEW: Sleep undergoes substantial changes during adolescence and suicide risk begins to increase during this period as well. This review focuses on recent literature on the relationship between sleep and suicidal behavior and proposes directions for future research. RECENT FINDINGS: Adolescent sleep is characterized by widespread sleep restriction, irregular sleep schedules, daytime sleepiness, and elevated risk for sleep disturbances. More research on adolescent sleep and psychosocial impairment, psychiatric disorders, and suicidal behavior has been conducted. Suicidal psychiatric patients had more sleep disturbances including insomnia, hypersomnia, or nightmares than nonsuicidal patients. Shorter rapid eye movement latency and increased rapid eye movement activity have been noted to be a marker of suicidality in psychiatric patients. Epidemiological studies have demonstrated that insomnia, nightmares, and sleep insufficiency are associated with elevated risk for suicide. Although the link between insomnia and suicidal behavior appears to be mediated by depression, existing data suggest an independent predictive role of nightmares in future suicidal behavior. SUMMARY: Sleep loss or disturbances are likely to signal an increased risk of future suicidal action in adolescents. Large-scale prospective studies and neurobiological studies are needed for a better understanding of the complex relationship between sleep, psychopathology, and youth suicidal behavior.     

Serial positron emission tomographic findings in an atypical presentation of fatal familial insomnia

BACKGROUND: Genetic analyses of fatal familial insomnia, a prion disease, disclose a broader range of symptoms than previously described. Although insomnia and dysautonomia have been described as hallmarks of the disease, there is substantial variability in clinical presentation. OBJECTIVE: To evaluate serial fluorodeoxyglucose positron emission tomographic and electroencephalographic findings in atypical fatal familial insomnia without clinical insomnia. PATIENT: A 63-year-old man who had a history of gait ataxia developed rapidly progressive dementia with mild dysautonomic features. Genetic investigation confirmed diagnosis of fatal familial insomnia (D178N mutation of the prion protein gene and Val/Met polymorphism on position 129 of the mutated allele) with typical neuropathologic findings. RESULTS: Clinical signs were not specific. An electroencephalogram showed scanty triphasiclike elements and general slowing. We found thalamic hypometabolism in positron emission tomographic scans to be present in a very early stage with progressive deterioration, and patchy cortical alterations showing progression over 6 months. CONCLUSIONS: In the absence of clear clinical signs, an electroencephalogram was of major diagnostic value, although its specificity in fatal familial insomnia is under debate. Selective thalamic hypometabolism seems to be an early marker in fatal familial insomnia, while cortical changes vary with clinical presentation and stage.     

Olivopontocerebellar degeneration, abnormal sleep, and REM sleep without atonia

Polygraphic studies during sleep performed in two patients with olivopontocerebellar degeneration (OPCD) revealed an abnormal control of muscle tone. It was demonstrated by bursts of EMG activity during sleep and progressive disappearance of muscle atonia during sleep. Muscle atonia disappeared during rapid eye movement (REM) sleep, permitting movements and expression of feelings probably associated with REM sleep-related oneiric activity. Patients, unaware of their nocturnal sleep disturbance, complained only of the resulting daytime tiredness and sleepiness.     

Sleep in psychiatric disorders

Altered sleep patterns are prominent in the majority of psychiatric disorders. This article examines the psychiatric disorders that are most often associated to sleep dysfunction as it is related in clinical practice and describes the polysomnographic findings. Patient's main complaints are related to difficulty in initiating and maintaining sleep (initial or middle insomnia, respectively) and poor quality of sleep. Early awakening or terminal insomnia is most described in the depressive conditions. Hypersomnia may be the main symptom in some depressive disorders, as seasonal depression, depression with atypical features or depressive episodes in bipolar disorder. Polysomnographic evaluation shows, in general, a significative reduction in the efficiency and total time of sleep, in detriment to the amount of slow wave sleep. The reduction of rapid eye movement (REM) sleep latency is mainly described for the depression, but has also been reported in other psychiatric disorders.     

Current management of sleep disturbances in dementia

The management of sleep disturbances in patients with dementia is a complicated and enormously important clinical and societal problem. In this review, we present one approach to the diagnosis and management of such sleep disturbances. Most disturbances can be categorized into four primary symptoms: insomnia, hypersomnia, excessive nocturnal motor activity, and hallucinations or behavioral problems. We describe how each symptom may relate to the dementing illnesses themselves, which primary sleep disorders may be at play, which medications employed for dementia may impact on the symptom, the role of depression in that symptom, and how circadian dysrhythmias can underlie that symptom. Although few well-designed studies have been conducted, we present management strategies for several sleep disturbances based on the literature and our clinical experience. Considering the impact on patient and caregiver quality of life, and the potential for delaying institutionalization with appropriate therapy, further research is clearly warranted to optimize the diagnosis and management of sleep disturbances in the cognitively impaired elderly population.     

Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder

Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT‐associated variants and the entire coding sequence of MAPT were analyzed. Age‐, sex‐, and ethnicity‐adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder. Results: MAPT‐H2 variants were associated with PD (odds ratios: 0.62‐0.65; P = 0.010‐0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12‐2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48‐0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. Conclusions: Our results confirm the protective effect of the MAPT‐H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society     

Prevalence and correlates of alpha-delta sleep in major depressive disorders

Objective. Major depressive disorder is associated with sleep disturbances. An electroencephalographic pattern of alpha wave intrusion in delta wave sleep (alpha-delta sleep) is observed in some subjects with major depressive disorder. The treatment-resistant symptoms in major depressive disorder, nonrestorative sleep and fatigue, are associated with alpha-delta sleep. The objective of this study is to identify the prevalence and clinical correlates of alpha-delta sleep in major depressive disorder.Design. Retrospective studySetting. Sleep Disorders Center, Cleveland Clinic, Cleveland, OhioParticipants. Polysomnograms were conducted on 150 subjects 18 years of age or older (75 with and 75 without major depressive disorder) were reviewed.Measurements. The percent of delta waves with alpha intrusion was collected and analyzed.Results. Subjects with major depressive disorder compared to nondepressed subjects had a higher sleep efficiency (83.0±9.6; 78.1±8.2%), shorter rapid eye movement latency (85.0±44.5; 189.9±25.6 min), less slow wave sleep (8.3±3.0; 13.5±6.2%), and greater rapid eye movement (24.7±7.0; 19.2±8.2%), and all of these findings were statistically significant. Patients with major depressive disorder had higher alpha-delta sleep (23.4±14.2%; 2.3±6.7%, p<0.01). Patients with major depressive disorder were categorized into high and low alpha-delta sleep based on percentage of alpha-delta sleep present in slow wave sleep (alpha-delta sleep was present ≥15% or ≤15% of slow wave sleep, respectively). Patients with major depressive disorder with high alpha-delta sleep were at 3.15 greater odds (1.22-8.14; p=0.018) to have excessive daytime sleepiness.Conclusion. Patients with major depressive disorder have a higher prevalence of alpha-delta sleep. Alpha-delta sleep is associated with daytime sleepiness in patients with major depressive disorder. Study limitations include the retrospective nature of the project and the fact that the principle investigator, who scored and interpreted alpha intrusion, was not blind to group membership.     

Agrypnia excitata: clinical features and pathophysiological implications

Fatal familial insomnia, Morvan's chorea and delirium tremens share the same clinical features: severe insomnia and mental confusion with dream enactment, associated with motor and autonomic activation. Polygraphically, they share an inability to generate slow wave sleep. Agrypnia excitata is the term which aptly defines this peculiar medical condition. In fatal familial insomnia, the syndrome is due to a functional imbalance between activating and deactivating structures within the limbic system provoked by the atrophy of the mediodorsal and anteroventral thalamic nuclei. In Morvan's chorea and delirium tremens, a functional imbalance within the thalamolimbic circuits might be explained by the accumulation of some antireceptor antibodies and by a transient prevalence of excitatory over inhibitory synapses, down-regulated by chronic alcohol abuse, respectively. The selective disappearance of slow sleep (i.e. sleep spindles and delta rhythms) characterizing the agrypnia excitata syndrome, together with other clinical and experimental findings, suggests that sleep can be divided into three types. The most archaic form of sleep corresponding to stage 1 non-REM sleep is shared by man and poikilothermic animals and generated within activating and deactivating neuronal poles located in the basal forebrain, hypothalamus and brain stem; the other two forms of sleep, slow wave sleep and paradoxical sleep, confined to homeothermic animals, are generated in the thalamus and pontine reticular formation respectively. 2001 Harcourt Publishers Ltd     

A note on the occurrence of unusual electroencephalographic sleep patterns in selected normal children.

Polysomnographic recordings were performed in 50 children free from any familial or personal history of seizure or neurologic diseases to evaluate the frequency of epileptiform and unusual electroencephalographic patterns in a normal population. A 9-year-old boy exhibited focal spikes that became bilateral with a density of 24% to 32% during slow wave sleep, and another boy showed a few spikes during slow wave sleep. In seven cases, 14- and 6-Hz rhythms were recorded, mostly in rapid eye movement sleep. A right rhythmic and temporal discharge was observed in one girl. Epileptiform electroencephalographic patterns are not infrequent, and 14- and 6-Hz rhythms during rapid eye movement sleep are common in normal children.