Loss Of Slow-wave Sleep Research Articles

Agrypnia excitata: a human model to explore the derailment of sleep-wake cycle integrated control.

The commemoration of the 70th anniversary of rapid eye movement sleep discovery offers a unique possibility to reassess the peculiar organic condition of agrypnia excitata. Agrypnia excitata is characterized by a severe loss of sleep leading to a complete derangement of physiological sleep-wake cycle and body homeostasis. Agrypnia excitata is a definite clinico-neurophysiological condition characterized by: (1) slow-wave sleep loss with disruption of sleepwake cycle; (2) a 24-hr motor and autonomic overactivity; and (3) peculiar episodes of oneiric stupor. Agrypnia excitata may happen within different pathophysiologies, such as delirium tremens, Morvan's syndrome and fatal familial insomnia, suggesting some general reflections on the composition and function of the cerebral neuronal network generating wake and sleep behaviour and regulating body homeostasis, with a focus on rapid eye movement sleep.

Sleep and local field potential effect of the D2 receptor agonist bromocriptine during the estrus cycle and postpartum period in female rats

BackgroundPituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion. MethodsSleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats. ResultsSleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments.Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments.Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing. ConclusionsThese results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.

Preventing cognitive decline using portable, non‐invasive sleep enhancement.

AbstractBackgroundRecently, disturbed slow wave sleep (SWS) has been identified as an early, modifiable risk factor for dementia. SWS is crucial for memory and metabolic clearance functions, and lack of SWS causes these important functions to suffer, which in turn worsens cognitive decline. A vicious cycle forms between cognitive decline and loss of SWS. Improving SWS could be a way to break this cycle by providing the much‐needed opportunity for the brain to recuperate and ameliorate cognitive decline. We aim to enhance slow wave activity in older adults using phase‐locked auditory stimulation (PLAS). Our laboratory‐based results show that the magnitude of the physiological response to PLAS predicts improvement of memory functions and metabolic clearance. However, larger, long‐term studies in an ecologically valid setting are needed to assess the efficacy of PLAS for the improvement of sleep, memory, and metabolic clearance with the goal of preventing cognitive decline. Laboratory‐based studies quickly become economically and logistically unfeasible to achieve this goal.MethodWe propose a blinded, sham‐controlled cross‐over study utilizing home‐use devices to study the effect of PLAS on memory functions in 60 older adults with MCI or SCD. Participants will undergo verum‐ and sham‐PLAS in the comfort of their own home across a 12‐week study period. Cognitive performance will be assessed using engaging “serious games”, and blood will be sampled before‐ and after each experimental period to test levels of dementia‐related biomarkers (amyloid beta, pTau181 and 217, GFAP and NfL) and their response to PLAS.ResultWe expect PLAS to enhance sleep, which will lead to down‐stream effects on memory performance and metabolic clearance. Using a novel approach allowing brain‐age estimation from sleep‐electrophysiology, we hypothesize to see a “rejuvenating” effect of PLAS, restoring an electrophysiological profile typically seen in younger brains.ConclusionThis study could pave the way for PLAS‐capable home‐use devices as an affordable, non‐invasive tool to combat cognitive decline, and could lead to novel preventative applications for memory clinics, relieving their clinical burden and improving public health.

Association Between Slow-Wave Sleep Loss and Incident Dementia

Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal. To determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss. This prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 2001 to 2003. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023. Changes in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years). Risk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG. From the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, -0.6 [1.5%] per year; P < .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG. This cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.

0074 Investigating the Impacts of Pharmacological Slow-Wave Sleep Enhancement on Cognition in an Alzheimer's Disease Model

Abstract Introduction Alzheimer’s disease (AD) is a debilitating and irreversible neurodegenerative disease associated with major disruptions to sleep. Recent works point to a strong bidirectional relationship between loss of slow-wave sleep (SWS), the deepest sleep stage, and the pathological and cognitive features of AD. Here, we investigate the impacts of chronic pharmacological SWS enhancement with gaboxadol, a delta GABAA receptor agonist, on cognitive performance the APP/PS1 mouse model of AD. Currently, we are assessing the impacts of this intervention on Abeta plaque burden. Methods Using electroencephalography (EEG), we first assessed if gaboxadol is capable of stimulating SWS sleep in 6-month-old AD mice. Next, 6-month-old control (CTRL) or AD mice received gaboxadol 5x/week for 4 weeks at the start of the light cycle. Groups underwent subsequent testing in the open field (OF), Y-maze, and contextual fear conditioning (CFC) assays (n = 8-9 mice per group). Data were analyzed using two- or three-way ANOVAs, with repeated measures when appropriate. Results Our EEG studies demonstrate that gaboxadol (6 mg/kg) significantly enhances SWS/NREM from baseline (p &amp;lt; 0.0308). Gaboxadol did not impact gross locomotor behavior assessed by distance travelled in the in the OF. However, rearing was decreased in AD mice compared to CTRL mice (p &amp;lt; 0.0128). In the Y-maze, gaboxadol significantly increased time spent in the novel arm in CTRL (p &amp;lt; 0.0386) but not AD mice. We did not find significant effects of gaboxadol on memory recall in the CFC assay. Conclusion Chronic pharmacological stimulation of SWS using gaboxadol does not show robust cognition-enhancing effects in APP/PS1 mice, but may be cognitively enhancing in CTRL mice. It is possible that longer treatment duration is necessary to rescue cognitive deficits in AD mice. Support (if any) NIA: 5R21AG064774-02 T32 GM7367-46

The promise of portable remote auditory stimulation tools to enhance slow-wave sleep and prevent cognitive decline.

Dementia is the seventh leading cause of mortality, and a major source of disability and dependency in older individuals globally. Cognitive decline (and, to a lesser extent, normal ageing) are associated with sleep fragmentation and loss of slow-wave sleep. Evidence suggests a bidirectional causal link between these losses. Phase-locked auditory stimulation has emerged as a promising non-invasive tool to enhance slow-wave sleep, potentially ameliorating cognitive decline. In laboratory settings, auditory stimulation is usually supervised by trained experts. Different algorithms (simple amplitude thresholds, topographic correlation, sine-wave fitting, phase-locked loop, and phase vocoder) are used to precisely target auditory stimulation to a desired phase of the slow wave. While all algorithms work well in younger adults, the altered sleep physiology of older adults and particularly those with neurodegenerative disorders requires a tailored approach that can adapt to older adults' fragmented sleep and reduced amplitudes of slow waves. Moreover, older adults might require a continuous intervention that is not feasible in laboratory settings. Recently, several auditory stimulation-capable portable devices ('Dreem®', 'SmartSleep®' and 'SleepLoop®') have been developed. We discuss these three devices regarding their potential as tools for science, and as clinical remote-intervention tools to combat cognitive decline. Currently, SleepLoop® shows the most promise for scientific research in older adults due to high transparency and customizability but is not commercially available. Studies evaluating down-stream effects on cognitive abilities, especially in patient populations, are required before a portable auditory stimulation device can be recommended as a clinical preventative remote-intervention tool.

Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample.

To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI. We studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression. Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, β [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, -0.12 [0.05], p = 0.010; percentage, -0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts. Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

Wide awake at bedtime? Effects of caffeine on sleep and circadian timing in male adolescents – A randomized crossover trial

Adolescents often suffer from short and mistimed sleep. To counteract the resulting daytime sleepiness they frequently consume caffeine. However, caffeine intake may exaggerate sleep problems by disturbing sleep and circadian timing. In a 28-hour double-blind randomized crossover study, we investigated to what extent caffeine disturbs slow-wave sleep (SWS) and delays circadian timing in teenagers. Following a 6-day ambulatory phase of caffeine abstinence and fixed sleep-wake cycles, 18 male teenagers (14–17 years old) ingested 80 mg caffeine vs. placebo in the laboratory four hours prior to an electro-encephalographically (EEG) recorded nighttime sleep episode. Data were analyzed using both frequentist and Bayesian statistics. The analyses suggest that subjective sleepiness is reduced after caffeine compared to placebo. However, we did not observe a strong caffeine-induced reduction in subjective sleep quality or SWS, but rather a high inter-individual variability in caffeine-induced SWS changes. Exploratory analyses suggest that particularly those individuals with a higher level of SWS during placebo reduced SWS in response to caffeine. Regarding salivary melatonin onsets, caffeine-induced delays were not evident at group level, and only observed in participants exposed to a higher caffeine dose relative to individual bodyweight (i.e., a dose > 1.3 mg/kg). Together, the results suggest that 80 mg caffeine are sufficient to induce alertness at a subjective level. However, particularly teenagers with a strong need for deep sleep might pay for these subjective benefits by a loss of SWS during the night. Thus, caffeine-induced sleep-disruptions might change along with the maturation of sleep need.

Fatal familial insomnia and Agrypnia Excitata: Autonomic dysfunctions and pathophysiological implications.

Fatal Familial Insomnia (FFI) is a hereditary prion disease caused by a mutation at codon 178 of the prion-protein gene leading to a D178N substitution in the protein determining severe and selective atrophy of mediodorsal and anteroventral thalamic nuclei. FFI is characterized by physiological sleep loss, which polygraphically appears to be a slow wave sleep loss, autonomic and motor hyperactivation with peculiar episodes of oneiric stupor. Alteration of autonomic functions is a great burden for FFI patients consisting in sympathetic overactivation, dysregulation of its physiological responses and disruption of circadian rhythms. The cardiovascular system is the most frequently and severely affected confirming the increased sympathetic drive with preserved parasympathetic responses. Sleep loss, autonomic and motor hyperactivation define Agrypnia Excitata (AE), which is not exclusive to FFI, but it has been canonically described also in Morvan Syndrome and Delirium Tremens. These three conditions present different pathophysiological mechanisms but share the same thalamo-limbic impairment of which AE is one of the possible clinical presentations. FFI, and consequently also AE, is a model for the investigation of the essential role of the thalamus in the organization of body homeostasis, integrating both sleep and autonomic function control.

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.

Intraindividual Variability of REM Sleep Behavior Disorder in Parkinson's Disease: A Comparative Assessment Using a New REM Sleep Behavior Disorder Severity Scale (RBDSS) for Clinical Routine

To develop a polysomnographic video-based scale for rating the severity of REM sleep behavior disorder (RBD), to classify the severity of RBD and to determine the intraindividual variability of RBD in patients with Parkinson disease (PD). Twenty PD patients identified with RBD were investigated with video-supported polysomnography (PSG). Seventy-three motor behavior events during REM sleep were graded visually and polysomnographically on an event-to-event basis according to categorical location of movements: "0" = no visible movement; "1" = slight movements or jerks "2" = movements involving proximal extremities, including violent behavior; "3" = axial involvement including bed falls. Vocalizations were rated as "1" for present or "0" for absent. Ratings were performed by 2 blinded raters. Reliability was calculated with Cohen's κ. Final RBD severity was determined by the highest score given. This rating scale was then used to compare RBD severity and density, calculated as RBD episodes per REM sleep minute over 2 consecutive nights in 10 additional PD patients with RBD. Statistical significance was determined by effect size (Hedges' g) and calculation of the confidence interval. Interrater reliability of the scale was 0.8 for movement data and 0.89 for vocalization data. Intraindividual RBD density varied significantly (effect size 0.5 ± 0.22; confidence interval 0.2 to 0.79) by factor 2.5 between the 2 PSG nights. Final RBD severity score differed in 60% of patients between nights 1 and 2. Forty percent of patients showed violent behavior, but only on one night. All patients had severely disturbed sleep with reduced sleep efficiency, loss of slow wave sleep, sleep fragmentation, and an increased periodic limb movement (PLM) index. The RBD severity scale (RBDSS) is a reliable, easy-to-use tool for assessing motor events during REM sleep with PSG. Severity and phenomenology of RBD shows a significant variability in the individual PD patient.

Sleep depth and fatigue: Role of cellular inflammatory activation

Individuals with underlying inflammation present with a high prevalence of non-specific co-morbid symptoms including sleep disturbance and fatigue. However, the association between cellular expression of proinflammatory cytokines, alterations of sleep depth and daytime fatigue has not been concurrently examined. In healthy adults (24–61 years old), evening levels of monocyte intracellular proinflammatory cytokine production were assessed prior to evaluation of polysomnographic sleep and measures of fatigue the following day. Stimulated monocyte production of interleukin-6 (IL-6), but not tumor necrosis factor α (TNF-α), was negatively associated with slow wave sleep (ΔR 2 = .17, p = .029). In contrast, stimulated monocyte production of IL-6 was positively associated with rapid-eye movement (REM) sleep duration during the first sleep cycle (ΔR 2 = .26, p < .01). Moreover, evening stimulated production of IL-6 was associated with fatigue the following day (ΔR 2 = .17, p = .05). Mediation analyses showed that slow wave sleep, but not REM sleep duration, mediated the relationship between evening levels of IL-6 production and daytime fatigue. These results indicate that increases in stimulated monocyte production of IL-6 may be associated with decreases in slow wave sleep and increases in REM sleep duration. Relative loss of slow wave sleep may be one pathway through which cellular inflammation leads to daytime fatigue.

Case report: Adult phenotype of Mulvihill–Smith syndrome

Mulvihill-Smith syndrome (MSS) is characterized by premature aging, multiple pigmented nevi, decreased facial subcutaneous fat, microcephaly, short stature, mental retardation and recurrent infections, however the adult phenotype of MSS has yet to be delineated. We report a 28-year-old woman with Mulvihill-Smith syndrome, who had a solid pseudopapillary cystic tumor of her pancreas at age 17 years. Her distinctive sleep pattern includes severe insomnia with disappearance of sleep spindles and K-complexes, persisting muscle tone, and loss of slow wave sleep. The clinical and neurophysiological studies are compatible with agrypnia excitata, a sleep disorder attributable to a dysfunction of the thalamo-limbic system. Brain magnetic resonance imaging and single photon emission computed tomography revealed structural and functional deficits in the dorsomedial region of the thalamus and indicated that an alteration in the thalamo-limbic system may underlie the sleep disturbances in MSS. Furthermore, the rapid and severe decline in acquired cognitive function showed the distinct cognitive impairments resembling dementia, including intellectual deficits, memory disorder and executive dysfunction. We posit that an early onset tumor, sleep disorder and cognitive decline are adult manifestations of Mulvihill-Smith syndrome.

“Agrypnia excitata” in a case of sporadic Creutzfeldt–Jakob disease VV2

Sporadic Creutzfeldt–Jakob disease (CJD) of the VV2 subtype (sCJDVV2) was diagnosed at autopsy in a 77-year-old man presenting with gait ataxia, daytime hypersomnolence and complex “oneiric” behaviours at wake–sleep transition....

Loss of Slow-Wave Sleep

A 40-year-old Hispanic American male, who weighed 165 lb and was 5’11” tall, consented to participate in a 3-day sleep protocol and was admitted to the UCLA General Clinical Research Center. The patient complained of fatigue during the day and difficulty initiating sleep, along with 3 to 4 awakenings per night. He denied snoring and having any difficulty breathing during sleep. A 2-week sleep diary confirmed his sleep-wake pattern. The patient also denied any history of head injury, epilepsy, or anoxia and the use of any over-the-counter or prescription medication use for the previous month. A diagnosis of current depression was ruled out, though he reported having been treated for depression with Paxil 2 years ago, when he took his last dose of Paxil. The patient reported alcohol consumption of 10 drinks per day, 12 days per month, with last his drink 18 days prior to study admission to the research center.

Fatal familial insomnia: a model disease in sleep physiopathology

Fatal Familial Insomnia (FFI) is characterized by loss of sleep, oneiric stupor with autonomic/motor hyperactivity and somato-motor abnormalities (pyramidal signs, myoclonus, dysarthria/dysphagia, ataxia). Positon emission tomography (PET) disclosed thalamic hypometabolism and milder involvement of the cortex; neuropathology severe neuronal loss in the thalamic nuclei variably affecting the caudate, gyrus cinguli and fronto-temporal cortices. Genetic analysis disclosed a mutation in the PRNP gene and FFI was transmitted to experimental animals, thus classifying FFI within the prion diseases. Rare Sporadic Fatal Insomnia (SFI) cases occur without PRNP mutation but with features similar to FFI. FFI represents a model disease for the study of sleep-wake regulation: (I) the profound thalamic hypometabolism/atrophy associated with lack of sleep spindles and delta sleep implicate the thalamus in the origin of slow wave sleep (SWS); (II) loss of SWS is associated with marked autonomic and motor hyperactivity; termed 'agrypnia excitata', this association has been proposed as a useful clinical concept representative of thalamo-limbic dysfunction; (III) lack of SWS occurs with substantial preservation of stage 1 NREM sleep, implying that the latter has mechanisms different from SWS and unaffected by thalamic atrophy; accordingly, conflating stage 1 NREM with SWS into NREM sleep is inappropriate.

Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery

Vigilance status was continually monitored in socially stable groups of rats exposed to the modified multiple platform (MMP) technique for sleep deprivation. For comparison, sleep parameters were also monitored in socially isolated rats deprived of sleep by the single platform (SP) method. In all cases, sleep was continuously recorded during baseline, during 96 h of sleep deprivation and during 4 days of recovery. Both multiple- and single-platform techniques completely abolished paradoxical sleep (PS) during the deprivation period, but also resulted in significant decreases in slow wave sleep (SWS) (−31% and −37%, respectively). Unexpectedly, animals on large platforms, which are normally intended as controls, also showed significant reductions in PS and SWS, and these effects were more pronounced in rats deprived in groups than in animals deprived in isolation. Another control preparation, rats placed on wire-mesh grids in the deprivation tank, also showed PS reduction (−39%) but no loss of SWS during the 4 test days. Paradoxical sleep rebound was observed in the first 24 h in all groups, except for grid controls. Overall, no significant differences were found between single- and multiple-platform procedures during the 4 days of deprivation. However, sleep rebound was more pronounced in MMP-deprived rats than in SP-deprived rats. Sleep loss in both control groups may reflect residual effect of stress that remain in the platform technique. These findings indicate that the MMP technique is effective in inducing PS deprivation (PSD). However, the fact that SWS is also affected may have implications for conclusions on paradoxical sleep function based upon paradoxical sleep deprivation.

Sleep deprivation as a probe of homeostatic sleep regulation in primary alcoholics

Background: Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marked loss of slow wave sleep that is even more profound in African American alcoholics as compared to European Americans. Using partial sleep deprivation, this study examined the extent to which abnormal sleep is reversible in alcoholic subjects. Methods: In a sample stratified on ethnicity, polysomnographic and spectral sleep EEG measures were compared in male primary alcoholic in patients ( n=46) and age-matched comparison controls ( n=32) at baseline—and recovery sleep following a night of partial sleep deprivation. Results: As compared to controls, alcoholic patients showed a loss of slow wave sleep and more spectral power in beta frequencies. Following sleep deprivation, slow wave sleep and delta power differentially changed between the groups. European American controls showed increases of slow wave sleep that were more robust than responses found in African American controls, whereas both alcoholic groups failed to show increases of slow wave sleep from baseline to recovery. Spectral EEG analyses revealed similar results; sleep deprivation induced significant increases of delta power during NREM-1 in the controls, but not in the alcoholics. Conclusions: Alcohol dependence compromises the augmentation of slow wave sleep and delta power seen in healthy adults following sleep deprivation. The differential effect of alcoholism on sleep stage physiology suggests a defect in the regulation or plasticity of slow wave sleep with implications for theories linking sleep depth to morbidity and outcome in alcoholics.

Agrypnia Excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep

Objectives: To analyse the clinicophysiological features of delirium tremens (DT), Morvan's fibrillary chorea (MC) and fatal familial insomnia (FFI) as representative of the new concept of Agrypnia Excitata (AE). Methods: DT, MC and FFI were compared for their clinical and polysomnographic features and, for MC and FFI, post-mortem verification. Results: DT, MC and FFI all display profound loss of slow-wave sleep (SWS) and abnormal rapid eye movement (REM) sleep with lack of muscular atonia and enacted dreams. Sleep spindles and K complexes are severely reduced. Motor overactivity is associated with increased sympathergic functions. Neuropathology discloses severe loss of neurons in the thalami and cingular areas in FFI, and leakage of antibodies in the thalamus in MC. Conclusions: Based on the similarities in DT, MC and FFI, we propose the new concept of AE as a clinical condition characterized by loss of SWS and abnormal REM sleep, associated with motor and autonomic sympathergic activation. AE is due to dysfunction of the thalamo-limbic system. Moreover, the preservation of light sleep in the face of severe loss of deep sleep in AE argues that 3 rather than the usually considered two (non REM and REM) independent states of sleep exist.

Cassette EEG sleep recordings in Gilles de la Tourette syndrome.

Tourette syndrome (TS) patients often complain of sleep problems, and questionnaire studies indicate that sleep disturbance is frequent. Decreased slow wave sleep and increased awakenings have been reported in laboratory polysomnography in TS patients, and a serotoninergic disorder of arousal has been postulated. We recorded outpatient sleep in 20 patients newly diagnosed with TS utilizing a 4-channel cassette EEG system. The newly-diagnosed patients were predominantly male, and ranged in age from 10 to 36 years. Some had taken psychotropic medications in the past, but none had been treated systematically for TS. Seven patients had chronic tics only, 8 had tics and attention deficit-hyperactivity, and 5 had tics plus obsessions and compulsions. None had other medical, neurologic, or psychiatric disorders. All were nocturnal sleepers, and were recorded in their usual sleeping environments and routines. TS patients had reduced sleep, decreased sleep efficiency, increased awakenings, and decreased slow wave sleep. Tic patients had increased nocturnal awakenings and movements, particularly those who had tics during sleep. Sleep fragmentation and loss of slow wave sleep was most marked in TS patients with attention deficit-hyperactivity. Sleep latency was increased, REM sleep reduced, and REM sleep latency decreased in TS patients with obsessions and compulsions. These findings accord with previous reports of sleep disturbance in TS, and suggest that these disturbances may vary with TS symptoms. Chronic tics may persist in sleep and cause awakenings, TS with attention deficit may be associated with a disorder of arousal and alertness, and obsessions and compulsions may be manifestations of a biochemical disturbance involving paradoxical sleep.