Alpha-delta Sleep Research Articles

Evaluation of the structural organization of sleep in obstructive apnea syndrome from the perspective of modern pathophysiology

To evaluate the features of structural organization of sleep in men 35-55 years of age with varying degrees of severity and duration of clinical manifestations of obstructive sleep apnea syndrome (OSAS) from the perspective of modern pathophysiology. The study included 49 male patients, aged 35-55 years (average age was 43.4±9.2 years), with a body mass index (BMI) of 33.64±1.2 kg/m2 with complaints of snoring of varying degrees of intensity, daytime sleepiness, arrest of breathing during sleep (according to others). The control group consisted of 15 healthy men who did not have complaints of sleep disorders and clinical manifestations of OSAS. The Pittsburgh sleep quality index (PSQI) questionnaire and polysomnographic monitoring study (PSG) were used. According to the results of the polysomnographic study, all patients were divided into 2 subgroups: 12 men of group 1with moderate OSAS (duration of clinical manifestations 4.5±1.0 years) and 37 men of group 2 with severe OSAS (duration 1.5±1.5 years). A decrease in the sleep quality was detected in 61.9% of patients in the group 1 and 89.2% of patients in the group 2. Significantly higher scores for the components of «sleep disturbance» and «daytime dysfunction» in patients with a longer duration of clinical manifestations were detected. Changes in the structure of sleep were identified in patients compared with controls. A statistically significant increase in WASO led to the reduction of sleep efficiency. In patients of group 2, a deficiency of the deep stages and REM-sleep was determined. There was a significant increase in the number of arousals in patients of both groups relative to the controls. Moreover, significant between-group differences were found. The short duration of OSAS symptoms causes a restructuring of the physiological system of sleep homeostasis to a different level of functioning with compensatory hyperfunction of the structures responsible for REM sleep and a decrease (economization) in the activity of anabolic processes during sleep due to a decrease in SWS, which is a characteristic feature of long-term adaptation. Severe course of OSAS leads to the appearance of specific phenomena of gross structural disorganization of sleep - «alpha-delta sleep» and disruption of its segmental organization, which shows the depletion and disruption of compensatory-adaptive mechanisms in the system of sleep homeostasis, disintegration and transformation of functional physiological system in the pathological condition.

Daytime Central Thalamic Deep Brain Stimulation Modulates Sleep Dynamics in the Severely Injured Brain: Mechanistic Insights and a Novel Framework for Alpha-Delta Sleep Generation.

Loss of organized sleep electrophysiology is a characteristic finding following severe brain injury. The return of structured elements of sleep architecture has been associated with positive prognosis across injury etiologies, suggesting a role for sleep dynamics as biomarkers of wakeful neuronal circuit function. In a continuing study of one minimally conscious state patient studied over the course of ~8½ years, we sought to investigate whether changes in daytime brain activation induced by central thalamic deep brain stimulation (CT-DBS) influenced sleep electrophysiology. In this patient subject, we previously reported significant improvements in sleep electrophysiology during 5½ years of CT-DBS treatment, including increased sleep spindle frequency and SWS delta power. We now present novel findings that many of these improvements in sleep electrophysiology regress following CT-DBS discontinuation; these regressions in sleep features correlate with a significant decrease in behavioral responsiveness. We also observe the re-emergence of alpha-delta sleep, which had been previously suppressed by daytime CT-DBS in this patient subject. Importantly, CT-DBS was only active during the daytime and has been proposed to mediate recovery of consciousness by driving synaptic activity across frontostriatal systems through the enhancement of thalamocortical output. Accordingly, the improvement of sleep dynamics during daytime CT-DBS and their subsequent regression following CT-DBS discontinuation implicates wakeful synaptic activity as a robust modulator of sleep electrophysiology. We interpret these findings in the context of the “synaptic homeostasis hypothesis,” whereby we propose that daytime upregulation of thalamocortical output in the severely injured brain may facilitate organized frontocortical circuit activation and yield net synaptic potentiation during wakefulness, providing a homeostatic drive that reconstitutes sleep dynamics over time. Furthermore, we consider common large-scale network dynamics across several neuropsychiatric disorders in which alpha-delta sleep has been documented, allowing us to formulate a novel mechanistic framework for alpha-delta sleep generation. We conclude that the bi-directional modulation of sleep electrophysiology by daytime thalamocortical activity in the severely injured brain: (1) emphasizes the cyclical carry-over effects of state-dependent circuit activation on large-scale brain dynamics, and (2) further implicates sleep electrophysiology as a sensitive indicator of wakeful brain activation and covert functional recovery in the severely injured brain.

Neurophysiological correlates of suicidal ideation in major depressive disorder: Hyperarousal during sleep

BackgroundSuicide is a major public health concern, and a barrier to reducing the suicide rate is the lack of objective predictors of risk. The present study considers whether quantitative sleep electroencephalography (EEG) may be a neurobiological correlate of suicidal ideation. MethodsParticipants included 84 (45 female, mean age=26.6) adults diagnosed with major depressive disorder (MDD). The item that measures thoughts of death or suicide on the Quick Inventory of Depressive Symptomatology (QIDS) was used to classify 47 participants as low suicidal ideation (24 females, mean age=26.1) and 37 as high suicidal ideation (21 females, mean age=27.3). Data were obtained from archival samples collected at the University of Michigan and University of Texas Southwestern Medical Center between 2004 and 2012. Sleep EEG was quantified using power spectral analysis, and focused on alpha, beta, and delta frequencies. ResultsResults indicated that participants with high compared to low suicidal ideation experienced 1) increased fast frequency activity, 2) decreased delta activity, and 3) increased alpha-delta sleep after adjusting for age, sex, depression, and insomnia symptoms. LimitationsLimitations include the exclusion of imminent suicidal intent, a single suicidal ideation item, and cross-sectional archival data. ConclusionsThis is one of the first studies to provide preliminary support that electrophysiological brain activity during sleep is associated with increased suicidal ideation in MDD, and may point toward central nervous system (CNS) hyperarousal during sleep as a neurobiological correlate of suicidal ideation.

Gender characteristics of the structural organization of sleep in obstructive sleep apnea syndrome

To reveal gender characteristics of the sleep structure in obstructive sleep apnea syndrome (OSAS) during polysomnographic monitoring (PSGM). According to the results of a pre-survey using an apnea screening questionnaire, the investigation included 58 women (body mass index (BMI), 38.2±2.1 kg/m2) and 75 men (BMI, 34.2±1.8 kg/m2), aged 50-55 years, who complained about snoring, sleep apnea, and daytime hypersomnia. Copy-pair groups were formed and compared after objectively confirming the diagnosis by PSGM made at a specialized sleep laboratory, by applying the GRASS-TELEFACTOR Twin PSG system (Comet) with an integrated SPM-1 sleep module (USA) in accordance with the standard procedure. The International Sleep Disorder Classification (2005) was used to diagnose apnea and to estimate its severity. According to the results of PSGM, the men and women were divided into 3 groups, by using the generally accepted OSAS severity scale. Comparative analysis revealed differences in sleep structure parameters with the equal severity of OSAS in the men and women. These differences were characterized by a more marked fragmentariness, impaired cyclicity, and the appearance of the basic specific phenomenon of impaired integrated activity of somnogenic structures - an alpha-delta sleep phenomenon in the men versus the women. There were increases in the time of rapid eye movement (REM) sleep, in that of awakening at night after falling asleep, and in sleep latency in the women with a simultaneous decrease in the total effectiveness of sleep compared to that in the men with the equal-severity OSAS. The found gender differences in the sleep structure may be ascribed to the compensatory mechanisms in the function of brain somnogenic structures in the women and the preponderance of REM sleep is a compensatory adaptive response of the sleep homeostatic system, which necessitates further investigations in this area.

Electroencephalographic patterns during sleep in children with chromosome 15q11.2-13.1 duplications (Dup15q).

Our objective was to define the EEG features during sleep of children with neurodevelopmental disorders due to copy number gains of 15q11-q13 (Dup15q). We retrospectively reviewed continuous EEG recordings of 42 children with Dup15q (mean age: eight years, 32 with idic15), and data collected included background activity, interictal epileptiform discharges, sleep organization, and ictal activity. Three patterns were recognized: Pattern 1: Alpha–delta sleep was noted in 14 children (33%), not associated with any clinical changes. Pattern 2: Electrical status epilepticus in sleep was noted in 15 children (35%), all diagnosed with treatmentresistant epilepsy. Thirteen of the 15 children had clinical seizures. Pattern 3: Frequent bursts of high amplitude bifrontal predominant, paroxysmal fast activity (12–15 Hz) during non-REM sleep was noted in 15 children (35%). All 15 children had treatment-resistant epilepsy. This is the first report of electroencephalographic patterns during sleep of children with Dup15q reporting alpha-delta rhythms, CSWS, and high amplitude fast frequencies. Alpha-delta rhythms are described in children with dysautonomia and/or mood disorders and CSWS in children with developmental regression. The significance of these findings in cognitive function and epilepsy for the children in our cohort needs to be determined with follow-up studies.

Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia.

Alpha-delta sleep is the abnormal intrusion of alpha activity (8- to 13-Hz oscillations) into the delta activity (1- to 4-Hz oscillations) that defines slow-wave sleep. Alpha-delta sleep is especially prevalent in fibromyalgia patients, and there is evidence suggesting that the irregularities in the sleep of these patients may cause the muscle and tissue pain that characterizes the disorder. We constructed a biophysically realistic mathematical model of alpha-delta sleep. Imaging studies in fibromyalgia patients suggesting altered levels of activity in the thalamus motivated a thalamic model as the source of alpha activity. Since sodium oxybate helps to alleviate the symptoms of fibromyalgia and reduces the amount of alpha-delta sleep in fibromyalgia patients, we examined how changes in the molecular targets of sodium oxybate affected alpha-delta activity in our circuit. Our model shows how alterations in GABAB currents and two thalamic currents, Ih (a hyperpolarization-activated current) and a potassium leak current, transform a circuit that normally produces delta oscillations into one that produces alpha-delta activity. Our findings suggest that drugs that reduce Ih conductances and/or increase potassium conductances, without necessarily increasing GABAB conductances, might be sufficient to restore delta sleep. Furthermore, they suggest that delta sleep might be restored by drugs that preferentially target these currents in the thalamus; such drugs might have fewer side effects than drugs that act systemically.

The acute effects of alcohol on sleep electroencephalogram power spectra in late adolescence.

Alcohol's effect on sleep electroencephalogram (EEG) power spectra during late adolescence is of interest given that this age group shows both dramatic increases in alcohol consumption and major sleep-related developmental changes in quantitative EEG measures. This study examined the effect of alcohol on sleep EEG power spectra in 18- to 21-year-old college students. Participants were 24 (12 female) healthy 18- to 21-year-old social drinkers. Participants underwent 2 conditions: presleep alcohol and placebo, followed by standard polysomnography with comprehensive EEG recordings. After alcohol, mean breath alcohol concentration at lights-out was 0.084%. Interaction effects indicated simultaneous increases in frontal non-rapid eye movement sleep (NREM) delta (p=0.031) and alpha (p=0.005) power in the first sleep cycles following alcohol consumption which was most prominent at frontal scalp sites (p<0.001). A decrease in sigma power (p=0.001) was also observed after alcohol. As hypothesized, alcohol increased slow wave sleep-related NREM delta power. However, there was a simultaneous increase in frontal alpha power. Results suggest that alcohol may exert an arousal influence which may compete with the sleep maintenance influence of increased delta activity. The phenomenon is similar to, or the same as, alpha-delta sleep which has been associated with the presence of disruptive stimuli during sleep. This may have negative implications for the impact of presleep alcohol consumption on sleep and consequent daytime functioning.

Sleep-wake time perception varies by direct or indirect query.

The diagnosis of insomnia rests on self-report of difficulty initiating or maintaining sleep. However, subjective reports may be unreliable, and possibly may vary by the method of inquiry. We investigated this possibility by comparing within-individual response to direct versus indirect time queries after overnight polysomnography. We obtained self-reported sleep-wake times via morning questionnaires in 879 consecutive adult diagnostic polysomnograms. Responses were compared within subjects (direct versus indirect query) and across groups defined by apnea-hypopnea index and by self-reported insomnia symptoms in pre-sleep questionnaires. Direct queries required a time duration response, while indirect queries required clock times from which we calculated time durations. Direct and indirect queries of sleep latency were the same in only 41% of cases, and total sleep time queries matched in only 5.4%. For both latency and total sleep, the most common discrepancy involved the indirect value being larger than the direct response. The discrepancy between direct and indirect queries was not related to objective sleep metrics. The degree of discrepancy was not related to the presence of insomnia symptoms, although patients reporting insomnia symptoms showed underestimation of total sleep duration by direct response. Self-reported sleep latency and total sleep time are often internally inconsistent when comparing direct and indirect survey queries of each measure. These discrepancies represent substantive challenges to effective clinical practice, particularly when diagnosis and management depends on self-reported sleep patterns, as with insomnia. Although self-reported sleep-wake times remains fundamental to clinical practice, objective measures provide clinically relevant adjunctive information.

Sleep characteristics in children with specific language impairment: macrostructure and microstrucrure analysis

Introduction Sleep is important for learning, memory and underlying neural plasticity. Studies support that children utilize a dual memory system when acquiring and integrating new vocabulary, and sleep (especially sleep spindles, slow waves sleep and REM sleep) is important for this process. We aimed to describe sleep characteristics in children with diagnosis of Specific Language Impairment because sleep disruption, especially of the microstructure, could have an important role in the development and evolution in these patients. Materials and methods 30 children (24 boys and 6 girls) with 3–5 years old, diagnosed of specific language impairment (development quotient ⩾ 70 in Brunet-Lezine Scale), normal MRI, without epileptiform discharges in EEG, no hearing impairment, no other disorders and with parents in medium–high sociocultural level. Children participated in a polysomnographic (PSG) sleep recording. Sleep disorders like Obstructive Sleep Apnea Pediatric (OSAP), Periodic Limb Movement Disorder (PLMD) and parasomnias, and sleep characteristics like sleep stages percentage, spindles characteristics, presence of significant alpha rhythm during sleep (alpha-delta sleep), microarousal index, sleep efficiency and awakenings episodes were analyzed. Results In our sample, we found OSAP only in one patient, and parasomnias in 2 patients. However, data about PLMD was relevant, 93.3% present this disorder with an average index of 9.316 ± 6.11 . We found an average of 4.073 % ± 3.41 of stage 1, 40.76 ± 8.89 of stage 2, 25.381 ± 6.91 of stage 3, 25.587 ± 6.91 of stage REM, 112.76 ± 25.65 of body movements, 3.10 ± 1.6 awakening episodes ⩾ 5 min, 85.14 ± 9.07 of sleep efficiency, 37.556 ± 9.6 of microarousal index (83.4% with microarousal index ⩾ 30 ), 80% present significant percentage of alpha rhythm during sleep and 66.7% presented unsuitable spindles. Conclusion We observed that although the sleep architecture in terms of the macrostructure, like time spent in the different stage of sleep, appears to not be consistently altered in relation with normal values, it is very important the analysis of sleep microstructure because specific features would be altered in these patients and could be related to the problem of language skills. Treatment for specific sleep disorders and treatment to stabilize sleep structure, could improve the symptomatology in these patients.

Dissociated sleep states in fibromyalgia: Prevalence and correlations

Introduction One of the prominent features in fibromyalgia patients (FMP) is the discrepancy between subjective and objective data. Pain index are more intense than in Rheumatoid Arthritis patients but supportive objective data are lacking. Sleep is among the most prevalent complaints and the intrusion of alpha activity, although common, is not specific. It may be considered that, somehow, the peripheral dysfunctions or complaints are magnified centrally. Therefore the objectives are: 1) To compare sleep and sleep questionnaires in FMP and healthy controls (HC); 2) To identify dissociated states (DS) in sleep microstructure,i.e., occurrence of alpha delta, NREM microevents in REM, presence of REMs and myoclonia in NREM. Materials and methods 20 FMP, mean age 44.00, and 14 HC, mean age 43.21, all females were evaluated with the following instruments: Type 1 PSG with 19 EEG electrodes, PSQI and Epworth Sleepiness scale (ESS). PSG were visually staged by experienced technicians and dissociated states were scored by a single technician. The percentage of DS (taking as reference the total number of sleep epochs per subject) was computed together with current sleep parameters. Student T test was used to evaluate differences between groups and Pearson correlation analysis was done to evaluated correlations between individual measures. Results Significant differences between groups are: Body Mass Index (FMP = 25.68; HC = 22.58); PSQI (FMP = 11.8; HC = 5.23); %N1 (FMP = 13.0; HC = 6.3); Microarousals (FMP = 37.8; HC = 40.4); Periodic Limb Movements of Sleep (PLMS) (FMP = 2.8; HC=.73); Alpha delta (AD) (FMP = 21.0; HC = 7.9); NREM myoclonia (FMP=.02; HC = 0.0); absence of DS (FMP = 76.8; HC = 90.6). Correlation analysis provided the following results: A- Sleep parameters: Total Sleep Time (TST) correlated with Time in bed (TIB), Sleep efficiency (SE), %N2, and negatively with %N3. SE correlates negatively with Sleep Latency (SL), REM latency (RL), %N1, Awakenings SL correlates with TIB, RL, %N1 RL correlates with TIB, Awakenings, PLMS, PSQI and negatively with %R %N1 correlates with Awakenings, PLMS, PSQI and negatively with %N3, % R %N2 correlates negatively with %N3, % R, ESS %N3 correlates with Awakenings, PSQI, ESS %R correlates negatively with Awakenings Apnea-Hypopnea Index (AHI) correlates with age PLMS correlates with PSQI ESS correlates with %N3 and negatively with %N2 B- DS parameters: AD correlates with Awakenings, %N2, Alpha REM (AR), REMs in NREM, REM without atonia and negatively with %R, ESS, absence of DS AR correlates with K-complex in REM and negatively with absence of DS Spindles in REM correlates with RL, Microarousals and NREM myoclonia REMs in NREM correlates with %N1, Awakenings, REM without atonia and negatively with ESS, absence of DS Microarousals correlates with NREM myoclonia NREM myoclonia correlates with Microarousals, PSQI, ESS REM without atonia correlates with RL, % N2, AD and negatively with %R, absence of DS Absence of DS correlates with %R, ESS and negatively with awakenings 1421. Conclusion Concerning our objectives it must be stated that the differences between groups are not overwhelming; the existent in term of polisomnography are mostly related with sleep microstructure. In fact FMP have decreased Microarousals, higher PLMS index and percentage of DS comparing with HC. FMP have also higher percentage of alpha delta sleep and NREM Myoclonia. In spite of this, and in line with the dissociation hypothesis, the subjective complaints evaluated by the PSQI are higher in FMP. The presence of dissociated states in sleep EEG is a further proof in favor of this hypothesis. The correlations found are in line with the general postulates of sleep organization. Acknowledgements Funded by: FCT project ”‘Detection of Brain Microstates in Fibromyalgia”’ (PTDC/SAU-BEB/104948/2008) Work supported by the technicians Joana Belo and Patricia Correia.

Relationship between Sleep and Pain in Adolescents with Juvenile Primary Fibromyalgia Syndrome

To investigate sleep quality in adolescents with juvenile primary fibromyalgia syndrome (JPFS) and determine whether sleep abnormalities, including alpha-delta sleep (ADS), correlate with pain intensity. We hypothesized that successful treatment for pain with exercise therapy would reduce ADS and improve sleep quality. Single-center preintervention and postintervention (mean = 5.7 ± 1.0 weeks; range = 4.0-7.3 weeks) observational study. Ten female adolescents (mean age = 16.2 ± 0.65 SD yr) who met criteria for JPFS and completed treatment. Multidisciplinary pain treatment, including intensive exercise therapy. Pain and disability were measured by a pain visual analog scale (VAS) and the functional disability inventory. Subjective sleep measures included a sleep VAS, an energy VAS, and the School Sleep Habits Survey. Objective sleep measures included actigraphy, polysomnography (PSG), and the Multiple Sleep Latency Test. Baseline PSG was compared with that of healthy age- and sex-matched control patients. At baseline, patients had poorer sleep efficiency, more arousals/awakenings, and more ADS (70.3% of total slow wave sleep [SWS] versus 21.9% SWS, P = 0.002) than controls. ADS was unrelated to pain, disability, or subjective sleep difficulty. After treatment, pain decreased (P = 0.000) and subjective sleep quality improved (P = 0.008). Objective sleep quality, including the amount of ADS, did not change. Although perceived sleep quality improved in adolescents with JPFS after treatment, objective measures did not. Our findings do not suggest exercise therapy for pain improves sleep by reducing ADS, nor do they support causal relationships between ADS and chronic pain or subjective sleep quality.

Light sleep and sleep time misperception – Relationship to alpha–delta sleep

We investigated the association of alpha-delta sleep (A-DS) with: (1) perception of light sleep and (2) discrepancy between subjective and objective sleep duration. We analyzed data from 5764 individuals who underwent polysomnography (PSG) and replied questions about quantity and quality of sleep, including sleep depth. The difference between objectively recorded sleep time and subjectively estimated sleep time was calculated. Alpha-delta sleep (A-DS) was visually scored in a scale from 1 to 4, based on the density and overnight duration of alpha activity and confirmed using spectral array of the electroencephalographic activity. A-DS scores 1-4 occurred in, respectively, 37.9%; 31.3%; 20.5%; and 6.2% of the cases. ANOVA showed significant difference of light sleep sensation (p<0.001) and sleep time underestimation (p<0.001) among the four A-DS categories. Regression to explain both light sleep and sleep time underestimation, controlling for confounders, confirmed A-DS as a significant regressor. This study of a large prospective sample provides evidence for the association of alpha-delta sleep with subjective sensation of light sleep and with sleep time underestimation. Alpha-delta sleep may be a marker of the physiological disorder underlying light sleep and sleep state misperception.

Fibromyalgia and sleep-disordered breathing: the missing link

Recently, Martinez-Lavin [1] proposed a model of sympathetically maintained neuropathic pain syndrome that has the merit of scrutinizing possible mechanisms behind the central sensitization model [2]. Eisinger [3], in an editorial comment, raises the issue of heterogeneity permeating Martinez-Lavin's proposition. Since it is difficult to establish a traumatic trigger event in all cases, Eisinger considers multicausality as more reasonable than a single post-traumatic etiology for all cases. Felix and Fontenele [4] further explored this venue, speculating that the orthostatic intolerance symptoms seen in the majority of fibromyalgia patients are a consequence of sympathetic hyperactivity. The idea that a COMT val-158-met polymorphism may cause higher cathecolamine levels has been explored [5]. Loevinger and colleagues [6] have shown that the metabolic syndrome is more common in individuals with fibromyalgia who also have higher body mass index, blood pressure, and waist-to-hip ratio than controls. Interestingly, elevated body mass index, blood pressure, and waist-to-hip ratio are associated with sleep-disordered breathing. We recently reported in a study that 50% of the women with obstructive sleep apnea syndrome or upper airway resistance syndrome had chronic pain and more than 11 tender points when pressed with 4 kgf/cm2 [7]. Guille-minault and colleagues [8] reported orthostatic intolerance in patients with upper airway resistance syndrome. We believe that the authors investigating this theme should discuss the possibility of sleep-disordered breathing being the missing link between fibromyalgia, pain, disturbed sleep, alpha-delta sleep, hypotension, sympathetic hyperactivity, and metabolic syndrome. We are conducting investigations into whether exposition to the typical stress of sleep-disordered breathing – with repeated arousal episodes and hypoxemia – has fibromyalgia as a possible outcome. Our preliminary results underline the need to consider and further explore this hypothesis.

Fibromyalgia and sleep-disordered breathing: the missing link – author's response

Fibromyalgia pathophysiology is a labyrinth where our understanding has grown from counting tender points to an evolving concept of subgroups and a countless variety of dysfunctional biochemical and metabolic interactions [1]. Sleep disorders have been reported in fibromyalgia patients [2], including daytime somnolence and tiredness, and non-restorative and fragmented sleep with higher occurrence of arousals, often associated with breathing-related disturbances. Electroencephalogram findings exhibit alpha-delta sleep and a reduction of slow-wave sleep [2,3]. More sophisticated studies may identify upper airway resistance syndrome or obstructive sleep apnea-hypoapnea syndrome associated with increased risk for cardiovascular events [4]. Conflicting results have been reported on the prevalence of fibromyalgia observed in patients with sleep apnea; it was significantly increased versus a control group according to Germanowicz [4], but was not according to Plantamura and colleagues [3]. It is noteworthy that Moldofsky [5], 30 years ago, demonstrated the induction of a musculoskeletal pain syndrome by selective deep sleep deprivation. These findings allow a better understanding of the subtle mechanisms of fibromyalgia, including decreased levels of serotonin and tryptophan, increased tumor necrosing factor alpha and interleukin 6 [4] or reduced growth hormone secretion. Recently, Martinez and Cassol [2] defined sleep-disordered breathing as a missing link between fibromyalgia, metabolic syndrome and orthostatic intolerance. Rather than a missing link, it could be one of the many links – mainly biological but also biomechanical, such as myofascial trigger points – that probably complicate the diagnosis and management of functional diseases and chronic pain. These fibrolinks were roughly summarized in complex figures presented at the Myopain 2007 congress in Washington DC, and have recently been published [7]. This labyrinth concerns: neurotransmitters or hormones; 'nociceptive' or 'antinociceptive' receptors [7]; inflammatory cytokines and insulin resistance [7]; glucose metabolism and nitric oxide/endothelin imbalance as well as apoptotic pathways or reactive oxygen species; and genetic disorders or neuro-vegetative disturbances [2]. Whatsoever, the rediscovery of the sleep-disordered breathing link deserves further investigation, in order to avoid or limit the eternal return of anti-depressant and anticonvulsivant therapies, which are often deceiving and, with respect to some recent drugs, poorly tolerated by fibromyalgia patients.

Defining the Occurrence and Influence of Alpha-Delta Sleep in Chronic Fatigue Syndrome

Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances. Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic descriptive statistical parameters were calculated. Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L. The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep.

Alpha-delta sleep in a patient with nocturnal panic attacks

We report here on our finding of an alpha-delta sleep in a 40-year-old-female patient suffering from panic attacks, including nocturnal panic attacks, who complained of non-restorative sleep. This finding suggests that sleep disturbance in a subgroup of patients suffering from panic disorder might be assessed by testing for a sleep electroencephalogram anomaly, as well as by assessing sleep structure according to the Rechtshaffen and Kales sleep stages.

Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C.

Subjects with Niemann-Pick disease, type C have been reported to display narcolepsylike symptoms, including cataplexy. In this study, 5 patients with juvenile Niemann-Pick disease were evaluted for sleep abnormalities using nocturnal polysomnography, clinical evaluation, and the Multiple Sleep Latency Test. HLA typing and cerebrospinal fluid hypocretin levels were also evaluated in 4 patients. Niemann-Pick disease diagnosis was confirmed in all cases biochemically and by the presence of foam cells in the bone marrow. Deterioration of intellectual function; the presence of pyramidal, dystonic and cerebellar features; and splenomegaly were observed in all cases. Cataplexy was reported in 1 patient. Nocturnal polysomnography revealed disrupted sleep in all patients. Total sleep time, sleep efficiency, rapid eye movement sleep, and delta sleep amounts were decreased when compared to age-matched controls. Altered sleep patterns included sudden increases in muscle tone during delta sleep, electroencephalographic sigma activity connected with rapid eye movements and muscle atonia, atypical K-complexes and spindle activity, and the presence of alpha-delta sleep. All Niemann-Pick disease cases exhibited fragmentary myoclonus. Shortened mean sleep latencies were observed in 3 patients during the Multiple Sleep Latency Test, but sleep-onset rapid eye movement periods were observed only in the case with cataplexy. This patient was HLA DQB1*0602 positive, while the other subjects were HLA negative. Cerebrospinal fluid hypocretin-1 levels were reduced in 2 patients (1 with cataplexy) while in the 2 other patients, the levels were at the lower range of the normal values. Hypocretin levels in the Niemann-Pick disease group (204.8 +/- 39.3 pg/mL) were significantly reduced when compared to controls (265.8 +/- 48.8 pg/mL). The findings suggest that lysozomal storage abnormalities in Niemann-Pick disease patients may impact the hypothalamus and, more specifically, hypocretin-containing cells. These changes might be partially responsible for sleep abnormalities and cataplexy in patients with Niemann-Pick disease.

The Symptoms and Signs of Upper Airway Resistance Syndrome: A Link to the Functional Somatic Syndromes

The functional somatic syndromes are associated with a variety of symptoms/signs of uncertain etiology. We determined the prevalence of several of those symptoms/signs in patients with sleep-disordered breathing and examined the relationship between the prevalence of the symptoms/signs and the severity of sleep-disordered breathing. A descriptive study without intervention. A university sleep-disorders center located in a suburban setting. Three groups of 25 consecutively collected patients with sleep-disordered breathing. Groups varied in their apnea hypopnea indexes (AHIs) as follows: upper airway resistance syndrome (UARS) [AHI < 10/h), mild-to-moderate obstructive sleep apnea/hypopnea (OSA/H) [AHI >or= 10 to < 40/h), and moderate-to-severe OSA/H (AHI >or= 40/h). Patients underwent comprehensive medical histories, physical examinations, and full-night polysomnography. The diagnosis of UARS included quantitative measurement of inspiratory airflow and inspiratory effort with demonstration of inspiratory flow limitation. The percentage of women among the patients with sleep-disordered breathing (p = 0.001) and the prevalence of sleep-onset insomnia (p = 0.04), headaches (p = 0.01), irritable bowel syndrome (p = 0.01), and alpha-delta sleep (p = 0.01) was correlated with decreasing severity of AHI group. We conclude that patients with UARS, mild-to-moderate OSA/H and moderate-to-severe OSA/H differ in their presenting symptoms/signs. The symptoms/signs of UARS closely resemble those of the functional somatic syndromes.

Fibromyalgia: symptom constellation and potential therapeutic options.

Fibromyalgia (FM) is a disease entity consisting of a heterogeneous cluster of symptoms that has thus far eluded identification of a causative etiology. The disease onset appears to follow physiological and/or psychological stressors and involves a subset of symptoms that are consistent with varied disorders found in multiple medical specialties to include rheumatology, immunology, endocrinology, neurology, and psychiatry. Owing to the heterogeneity of the symptom complex and the heretofore absence of serum markers that might serve as concrete diagnostic criteria, this disease has baffled clinicians and basic scientists alike. Recent findings regarding sleep architecture, immunology, and endocrinology have provided clues that may help in the understanding and resultant treatment of this entity. Women with fibromyalgia tend to present with an alpha-delta sleep anomaly, which when treated with a growth hormone secretagogue (GHS), reduces the rheumatological pain and restores slow-wave sleep architecture. These findings suggest the somatotrophic axis may be involved in the etiology and the treatment of this disorder. Those diagnosed with FM respond to various stressors with increased disruption of their physiological homeostasis. When compared to healthy age-matched cohorts, there are quantitative differences in various neuroactive steroid levels, immunological markers, and feedback mechanisms. The varied physiological alterations in patients diagnosed with fibromyalgia when compared to controls will be discussed along with the potential treatment options for this population.

Limbic activity in slow wave sleep in a healthy subject with alpha–delta sleep

All-night electroencephalographic (EEG) activity was recorded in a healthy subject with known alpha–delta sleep. Recordings were made from all 19 of the 10/20 system electrode sites, and low resolution electromagnetic tomography (LORETA) was used to estimate intracerebral current densities. Sleep stages were compared within classical frequency bands by statistical parametric mapping (SPM). With the onset of sleep, occipital alpha abated. With increasing depth of sleep, alpha power increased in a region comprising the left frontal lobe, the anterior and parietal cingulum, and the anterior and medial right front lobe. In slow wave sleep (SWS), frontal alpha power was much greater than in wakefulness. The maximum of frontal alpha power of SWS was localised symmetrically in the left and right anterior cingulum. The observed alpha activity was different from the occipital alpha characteristic of wakefulness; it was a distinct activity of separate origin. The anterior limbic lobes seemed to play an active part in SWS in this healthy volunteer with an alpha–delta sleep pattern.