[Abnormal nocturnal behavior mimicking REM sleep behavior disorder episodes in a patient with periodic limb movement disorder].

Periodic limb movement disorder (PLMD) is a condition in which patients experience frequent periodic limb movements of sleep (PLMS). Synchronized arousal responses cause sleep fragmentation, resulting in insomnia, daytime sleepiness, and fatigue. A 59-year-old man was identified as having intense sleep-talking and body movements, suggesting rapid eye movement (REM) sleep behavior disorder (RBD). Attended video-polysomnography (PSG) revealed that sleep-talking and body movements occurred only during non-REM sleep and were associated with PLMS-induced arousals (periodic leg movement arousal index, 53.2/h). Pramipexole administration improved events during sleep and daytime sleepiness, and the PSG findings and clinical course led to a diagnosis of PLMD. This case demonstrates that PLMD mimics the symptoms of RBD and that a detailed analysis of monitored video PSG is crucial to confirm the diagnosis of RBD and to identify or exclude other causes of sleep talking and behavior.

Relationships between respiratory and oromotor events differ between motor phenotypes in patients with obstructive sleep apnea.

Purpose: The present study investigated the relationship between sleep bruxism (SB) and obstructive sleep apnea (OSA) in relation to the sleep architecture. Methods: We conducted a cross-sectional study. Polysomnographic recordings were performed on 36 patients. Sleep, respiratory, and oromotor variables, such as rhythmic masticatory muscle activity (RMMA) and non-specific masticatory muscle activity (NSMA), were compared between OSA patients with or without SB. A correlation analysis of the frequency of respiratory and oromotor events in NREM and REM sleep was performed. The frequency of oromotor events following respiratory events was also assessed. Results: The proportion of REM sleep was higher in OSA patients with SB than in those without SB (p = 0.02). The apnea-hypopnea index (AHI) did not significantly differ between the two groups; however, AHI was approximately 8-fold lower during REM sleep in OSA patients with SB (p = 0.01) and the arousal threshold was also lower (p = 0.04). Although the RMMA index was higher in OSA patients with than in those without SB (p < 0.01), the NSMA index did not significantly differ. The percentage of RMMA following respiratory events was significantly higher in OSA patients with than in those without SB, whereas that of NSMA did not significantly differ. The frequency of oromotor events throughout the whole night positively correlated with AHI. However, regardless of the sleep state, AHI did not correlate with the RMMA index, but positively correlated with the NSMA index. Conclusion: In consideration of the limitations of the present study, the results obtained indicate that OSA patients with SB have a unique phenotype of OSA and also emphasize the distinct relationship of respiratory events with RMMA and NSMA.

A lack of specific motor patterns between rhythmic/non-rhythmic masticatory muscle activity and bodily movements in sleep bruxism.

Purpose The aims of the present study were to investigate the temporal relationships between jaw and bodily movements and clarify motor processes in the genesis of rhythmic masticatory muscle activity (RMMA) in sleep bruxism (SB).Methods Video-polysomnography recordings were obtained from ten subjects with SB (mean age: 23.4 ± 1.6 years) and ten matched normal controls (CTL) (mean age: 24.4 ± 3.2 years). RMMA and nonspecific masseter activity (NSMA) were scored in association with bodily movements in the leg, arm, head, and trunk using electromyography and video recordings. The relationship between oromotor episodes and bodily movements was assessed in terms of sleep stage distributions and temporal relationships. Cardiac changes preceding oromotor episodes in stage N2 were assessed.Results Approximately 80% of RMMA and NSMA were associated with movements in one or more body sites. RMMA and NSMA were more frequently associated with movements of the leg (70-75%) and arm (40-55%) than movements of the head (17-22%) and trunk (5-25%). The relationship between oromotor episodes and bodily movements did not significantly differ among sleep stages. Oromotor episodes and bodily movements did not show a consistent temporal pattern in the SB and CTL groups. Regardless of the temporal relationship between oromotor episodes and bodily movements, the mean heart rate significantly increased by 5 beats before the onset of oromotor episodes.Conclusions No specific temporal motor patterns were found between RMMA and bodily movements. RMMA and NSMA represent a repertoire of arousal-related autonomic motor responses during sleep.

Polysomnographic analysis of respiratory events during sleep in young nonobese Japanese adults without clinical complaints of sleep apnea.

STUDY OBJECTIVES: The present study aimed to investigate the occurrence and characteristics of apnea-hypopnea events in young nonobese healthy Japanese participants. METHODS: One hundred and three young adult participants without sleep complaints (men: 56; women: 47; age: 24.5 ± 3.0 years; body mass index: 20.9 ± 1.8 kg/m²) underwent 2-night polysomnography. Data on the 2nd night were scored according to American Academy of Sleep Medicine criteria version 2.1. The apnea-hypopnea index (AHI) was estimated. The arousal threshold was calculated in participants with AHI ≥ 5 events/h. Apnea-hypopnea events were rescored by 3 other criteria issued by the American Academy of Sleep Medicine (AASM): Chicago criteria in 1999 and recommended and alternative criteria in 2007. RESULTS: Participants had good sleep characterized by high sleep efficiency (93.2%). Mean AHI of AASM 2.1 recommended criteria was 4.0 ± 5.3 events/h. AHI was significantly higher in men (median [range] = 4.0[.3-35.8] events/h) than in women (1.6 [.1-18.1] events/h). The prevalence rates of AHI ≥ 5 events/h and ≥ 15 events/h were 25.2 and 3.9%, respectively. The arousal threshold was estimated as -7.7 ± 2.6 cm H2O. AHI was lower for AASM 2007 recommended criteria (.8 [.0-18.2 events/h]) and AASM 2007 alternative (2.0 [.1-32.2] events/h) than for AASM version 2.1 recommended criteria (2.4 [.1-32.9] events/h) and AASM Chicago (4.6 [.1-35.8] events/h). The percentage of participants with AHI ≥ 5 events/h was approximately 2-fold higher with AASM Chicago (44.6%) than with AASM version 2.1 recommended criteria. CONCLUSIONS: The present study demonstrated that 25% of young nonobese Japanese participants had subclinical obstructive sleep apnea. The presence of frequent airflow limitations may be a risk factor for the development of obstructive sleep apnea in Japanese individuals.

Rate of augmentation and risk factors with long-term follow-up in Japanese patients with restless legs syndrome.

OBJECTIVES: Preventing augmentation is the critical clinical issue for RLS treatment. As for augmentation in Asian RLS patients, there have been only four studies and the follow-up durations of these studies were not long. We investigated Japanese RLS patients with longer duration of treatment in a clinical setting. METHODS: This study is a retrospective assessment of 42 RLS patients with follow-up durations of longer than 18 months (78.4 ± 29.2, range 19-139) at two urban sleep centers in Osaka, Japan from May 2004 to April 2014. RESULTS: The mean age of first visit was 63.5 ± 14.1 years old and the estimated age of RLS onset was 47.9 ± 16.5 years old. Twenty-eight out of 42 patients were female. At initial evaluation, the mean International Restless Legs Scale score (IRLS score) was 22.0 ± 5.9. Thirty-one of 42 had already visited other clinics before coming to our sleep centers, and the number of clinics visited was 1.3 ± 0.6. Augmentation developed in two patients (4.8%), and the dosage of dopamine equivalent in patients with and without augmentation was 12.5 and 18.8 mg vs. 15.8 ± 17.7 mg. In the two RLS patients with augmentation, ferritin was 113.1 and 114.1 ng/mL, respectively, and the number of clinics before coming to our sleep centers was both three. CONCLUSIONS: The augmentation rate of Japanese RLS patients from our study is low compared with previous Western and Asian studies. It might be attributable to racial difference, lower dosage of dopaminergic treatment, and the level of ferritin.

[A case of severe obstructive sleep apnea mimicking REM sleep behavior disorder].

The rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behaviors related to the loss of the normal generalized skeletal muscle atonia during REM sleep, and shows REM sleep without atonia (RWA) during polysomnography (PSG). Patients with idiopathic RBD have been known to have a siginificantly increased risk of developing one of the α-synucleiopathies later in life, therefore the diagnosis of RBD is very important and must be dealt with carefully. A 51-year-old man was identified presenting dream-enacting behaviors and unpleasant dreams suggesting the diagnosis of RBD, in addition to snoring and excessive daytime sleepiness. Attended video-PSG excluded RBD showing REM sleep with atonia and without increased phasic EMG activity, and diagnosed with severe obstructive sleep apnea (OSA) with an apnea-hypopnea index of 30.1 demonstrating that the reported abnormal sleep behaviors occurred only during respiratory event-induced arousals. Continuous positive airway pressure therapy eliminated the abnormal behaviors, unpleasant dreams, snoring and daytime hypersomnolence. This case shows that severe OSA mimic the symptoms of RBD and that attended video-PSG is necessary to establish the diagnosis of RBD, and identify or exclude other causes of dream-enacting behaviors.

Subjective oropharyngeal symptoms for abnormal swallowing in Japanese patients with obstructive sleep apnea syndrome: a descriptive questionnaire study.

OBJECTIVES: This study aimed to investigate the prevalence of clinical symptoms related to abnormal swallowing in a large sample of obstructive sleep apnea syndrome (OSAS) patients. METHODS: Oropharyngeal symptoms for abnormal swallowing were assessed by a self-administered questionnaire in 507 consecutive patients (females: 65, males: 442; mean age: 49.6 ± 12.6 years old) with clinical symptoms of OSAS, enrolled for cardiorespiratory evaluation. RESULTS: Overall, 16.2% of patients (82/507) had at least one symptom for abnormal swallowing and 6.3% (32/507) had two or more symptoms. The most frequent symptom was difficulty with coughing up phlegm during or after a meal (8.3%). Demographic, sleep, and clinical variables did not differ between the patients with and without abnormal symptoms. CONCLUSIONS: The results of the current study showed that 16% of middle-aged OSAS patients reported pharyngeal symptoms related to abnormal swallowing, regardless of the severity of OSAS.

Responsiveness of jaw motor activation to arousals during sleep in patients with obstructive sleep apnea syndrome.

OBJECTIVES: We aimed to characterize the association between jaw muscle contractions and respiratory events in patients with obstructive sleep apnea syndrome (OSAS) and to investigate the responsiveness of the contractions to respiratory events in comparison with that of leg muscles in terms of arousal types and sleep states. METHODS: Polysomnographic (PSG) recordings were performed in 19 OSAS patients (F/M: 2/17; 53.1 ± 13.7 years; AHI: 31.8 ± 19.9/h) with no concomitant sleep bruxism or other sleep-related movement disorders. Muscle contractions of unilateral masseter (MAS) and anterior tibialis (AT) muscles were scored during sleep in association with graded arousals (microarousals and awakenings) related or unrelated to apneahypopnea events. RESULTS: Arousals were scored for 68.2% and 52.3% of respiratory events during light NREM and REM sleep, respectively. Respiratory events with arousals were associated with longer event duration and/or larger transient oxygen desaturation than those without (ANOVAs: p < 0.05). Median response rates of MAS events to respiratory events were 32.1% and 18.9% during NREM and REM sleep. During two sleep states, MAS muscle was rarely activated after respiratory events without arousals, while its response rate increased significantly in association with the duration of arousals (Friedman tests: p < 0.001). A similar response pattern was found for AT muscle. Motor responsiveness of the two muscles to arousals after respiratory events did not differ from responsiveness to spontaneous arousals in two sleep stages. CONCLUSION: In patients with OSAS, the contractions of MAS and AT muscles after respiratory events can be nonspecific motor phenomena, dependent on the duration of arousals rather than the occurrence of respiratory events.

Negative association between self-reported jaw symptoms and apnea-hypopnea index in patients with symptoms of obstructive sleep apnea syndrome: a pilot study.

OBJECTIVES: Prior to oral appliance therapy for snoring and obstructive sleep apnea syndrome (OSAS), patients are screened for jaw symptoms (e.g., pain). However, the presence of jaw symptoms in a large spectrum of OSAS patients remains unknown. This study aimed to assess the distribution of subjective jaw symptoms in patients with symptoms of OSAS. METHODS: Five hundred and eleven consecutive patients (66 female, 445 male; mean age 49.6 ± 12.6 years) with clinical symptoms of OSAS were enrolled for cardiorespiratory evaluation. Self-administered questionnaires were used to assess jaw symptoms, tooth grinding and clenching during sleep, morning oral dryness, morning heartburn sensation, and pain in the neck and back. RESULTS: The mean apnea-hypopnea (AHI) index was 32.5 ± 30.6 per hour of sleep. Nineteen percent of patients (n = 96) reported at least one jaw symptom. The presence of jaw symptoms was more frequently reported by patients with AHI less than 15 (25 %) than those with AHI of 15 and more (15 %, p = 0.012). In the crude analyses, jaw symptoms were associated with tooth grinding, tooth clenching, morning oral dryness, morning heartburn sensation, and neck/back pain. Multiple logistic regression analysis confirmed that jaw symptoms were associated with AHI less than 15 (odds ratio (OR) 1.99, p = 0.009), tooth clenching (OR 1.79, p = 0.006), morning oral dryness (OR 2.17, p = 0.02), and neck/back pain (OR 1.99, p = 0.005). CONCLUSIONS: Jaw symptoms can be found in 19 % of patients with symptoms of OSAS and are more frequently reported in patients with lower AHI, a patient population for whom oral appliances are often prescribed.

[Case of exploding head syndrome].

Exploding head syndrome (EHS) attacks are characterized by the sensation of sudden loud banging noises, and are occasionally accompanied by the sensation of a flash light. Although these attacks in themselves are usually not painful, it is reported that EHS attacks may precede migraines and may be perceived as auras. A 53-year-old woman, with a 40-year history of fulgurating migraines, experienced 2 different types of EHS attacks. During most of the attacks, which were not painful, she heard sounds like someone yelling or cars passing by. Only 1 episode was accompanied with the sensation of a flash light and of sounds similar to those of an electrical short circuit. On the video-polysomnography, video-polysomnography showed 11 EHS attacks occurred during stage N1 and stage N2; these attacks were preceded by soft snoring. She also had moderate obstructive sleep apnea syndrome (Apnea Hypopnea Index: 16.7) for which an oral appliance was prescribed; the EHS attacks did not recur after this treatment. The pathophysiology of EHS is still unclear. A detailed analysis of PSG data may help in understanding the pathophysiology of this syndrome and also in the selection of therapeutic strategies.

[Demographic characteristics of RBD patients at a sleep center--with special emphasis on neurodegenerative diseases as the background condition].

UNLABELLED: REM sleep behavior disorder (RBD) is characterized by loss of normal REM sleep skeletal muscle atonia, resulting in complex motor behaviors associated with dream mentation. Reports have been accumulated showing an association of RBD and neurodegenerative diseases. However, in Japan, no data has been available about demographic features of RBD in a large patient population. We describe demographic characteristics of RBD patients presenting to our sleep center with special emphasis on association of RBD and neurodegenerative diseases. METHODS: The subjects were consecutive 10,745 patients who presented with sleep and/or wake problems at our sleep center from April 1998 to March 2006. Diagnosis of RBD was made based on ICSD-2 criteria. Medical and sleep histories with complementary information from family members, and findings of neurological examination were assessed retrospectively from the notes of RBD patients. RESULTS: Sixty-seven patients (0.6%) were diagnosed as having RBD. There was strong male predominancy (85.1%). The onset of RBD symptoms was at 61.4+/-8.8 years of age. Neurological symptoms and signs were present in twelve (17.9 % of RBD patients) when they firstly came to our sleep center: 4 patients with Parkinson disease, 4 with multiple system atrophy and 1 with probable dementia with Lewy body. Thirteen patients (43.3%) were aware of olfactory impairment when inquired (out of 30 patients). Clonazepam was administered in 29 patients, and 21 (72.4%) responded well. CONCLUSION: Our study showed the similar demographic characteristics of RBD to what was shown in the previous large case series. Although the association between RBD and neurodegenerative diseases was not so strong in our cases, it may be mainly because our sleep center was not run in the domain of neurology department and we could not vigorously detect the possible coexistence of neurodegenerative disease. The pathogenesis of RBD is still unclear; therefore, neurologists and sleep specialists need to collaborate in following up RBD patients to confirm whether they are at higher risk for developing a neurodegenerative disease.

The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men.

STUDY OBJECTIVES: Elevated C-reactive protein (CRP), an inflammatory marker and emerging risk factor for atherosclerosis and coronary heart disease, has been reported in overweight patients with sleep-disordered breathing (SDB). However, the contribution of C-reactive protein to this disease among non-overweight individuals is uncertain. We thus examined the relationship between serum C-reactive protein levels and nocturnal arterial oxygen desaturation, stratified by category of body mass index (BMI). DESIGN: Cross-sectional study. PARTICIPANTS: Subjects were 316 men with a mean BMI of 25.4 kg/m2, aged 20-79 years, who attended a sleep clinic at Osaka, Japan. MEASUREMENTS AND RESULTS: SDB was assessed by oxygen desaturation index (ODI) measured by pulse oximetry during sleep. We used 3% oxygen desaturations per hour (3% ODI), as the indicator of SDB. We also measured serum levels of C-reactive protein (CRP). After adjustment for age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking status, alcohol consumption, and daily sleep duration, mean high-sensitivity CRP levels were 0.63, 0.65, and 0.96 mg/L for SDB severity levels of 3%ODI<5, 5 to 19.9, and >=20, respectively (p for trend=0.015). This association with SDB tended to be stronger in non-overweight men (BMI<25 kg/m2) (0.47, 0.48 and 1.02 mg/L, p for trend=0.017) than in overweight men (BMI > or = 25 kg/m2) (0.92, 0.87 and 1.21 mg/L, p for trend=0.11). CONCLUSION: SDB is associated with increased levels of CRP, especially in non-overweight men. Our results suggest the importance of follow-up and control of SDB in the prevention of cardiovascular disease even in non-overweight SDB patients.

Relationships of craniofacial morphology and body mass index with sleep-disordered breathing in Japanese men.

OBJECTIVE/HYPOTHESIS: Obesity is an established risk factor for sleep-disordered breathing, but the impact of craniofacial morphology is uncertain. The aim of this study was to assess the impact of craniofacial morphology and body weight on sleep-disordered breathing in Japanese men. STUDY DESIGN: A cross-sectional study. METHODS: We measured body mass index, seven cephalometric variables, and 3% oxygen desaturation index recorded by a pulse oximeter in 313 Japanese men aged 20 to 65 years who attended a sleep clinic. We defined craniofacial score as the sums of quartile points (0-3) for distance from sella to nasion and that from hyoid bone to mandibular plane. RESULTS: The mean value of 3% oxygen desaturation index and odds ratios of 3% oxygen desaturation index 15 or greater progressively increased with craniofacial score as well as body mass index. Multivariate odds ratios associated with craniofacial score were higher in men with body mass index 25.0 kg/m or greater (odds ratio = 4.2, 95% confidence interval [CI] = 2.1-8.6) than in men with lower body mass index (odds ratio = 1.6, 95% CI = 0.7-3.6). CONCLUSIONS: Our results imply the importance of cephalometric assessment in overweight patients.

The roles of midbrain and diencephalic dopamine cell groups in the regulation of cataplexy in narcoleptic Dobermans.

Cataplexy, an emotion-triggered sudden loss of muscle tone specific to narcolepsy, is tightly associated with hypocretin deficiency. Using hypocretin receptor 2 gene (hcrtr 2)-mutated narcoleptic Dobermans, we have previously demonstrated that altered dopamine (DA) D(2/3) receptor mechanisms in mesencephalic DA nuclei are important for the induction of cataplexy. In the current study, we also found that the administration of D(2/3) agonists into diencephalic dopaminergic cell groups, including the area dorsal to the ventral tegmental area (DRVTA) and the periventricular gray (PVG) matter of the caudal thalamus (corresponding to area A11), significantly aggravated cataplexy in hcrtr 2-mutated narcoleptic Dobermans. A D(1) agonist and antagonist and a DA uptake inhibitor perfused into the DRVTA had no effect on cataplexy, suggesting an involvement of D(2/3) receptors located on DA cell bodies (i.e., autoreceptors) for the regulation of cataplexy. Because the A11 cell group projects to the spinal ventral horn, the A11 D(2/3) receptive mechanisms may directly modulate the activity of spinal motoneurons and modulate cataplexy.

Novel variants of murine serotonin transporter mRNA and the promoter activity of its upstream site.

Three variants of murine serotonin transporter (5-HTT) mRNA, which consist of a different exon-one (exon 1a, exon 1b or exon 1c) and the same exon-two to exon-five, were identified. The promoter region for each exon 1 (p1a, p1b and p1c, respectively), ligated to pGL-3 enhancer vector, had activities significantly higher than the empty vector in all cell lines tested except p1c in PC-12, whereas the activity of p1c was significantly lower than the others. Effects of the treatment of dibutyryl-cyclic AMP, human interferon-alpha or mouse interferon-gamma have different profiles among COS-7, PC-12, C6 glioma and immortalized rat serotonergic raphe neurons, RN46A. These three promoter regions may play a role in the transcription of the 5-HTT and could offer a model of the regulation of 5-HTT production in humans and further the pathogenesis of depression.

Narcolepsy: genetic predisposition and neuropharmacological mechanisms. REVIEW ARTICLE.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime somnolence (EDS), cataplexy and REM sleep-related abnormalities. It is a frequently-occurring but under-diagnosed condition that affects 0.02 to 0.18% of the general population in various countries. Although most cases occur sporadically, familial clustering may be observed; the risk of a first-degree relative of a narcoleptic developing narcolepsy is 10-40 times higher than in the general population. The disorder is tightly associated with the specific human leukocyte antigen (HLA) allele, DQB1*0602 [most often in combination with HLA-DR2 (DRB1*15)]. Genetic transmission is, however, likely to be polygenic in most cases, and genetic factors other than HLA-DQ are also likely to be implicated. In addition, environmental factors are involved in disease predisposition; most monozygotic twins pairs reported in the literature are discordant for narcolepsy. Narcolepsy was reported to exist in canines in the early 1970s. Both sporadic and familial cases are also observed in this animal species. A highly-penetrant single autosomal recessive gene, canarc-1, is involved in the transmission of narcolepsy in Doberman pinschers and Labrador retrievers. Positional cloning of this gene is in progress, and a human homologue of this gene, or a gene with a functional relationship to canarc-1, might be involved in some human cases. Human narcolepsy is currently treated with central nervous system (CNS) stimulants for EDS and antidepressants for cataplexy and abnormal REM sleep. These treatments are purely symptomatic and induce numerous side effects. These compounds disturb nocturnal sleep in many patients, and tolerance may develop as a result of continuous treatment. The canine model is an invaluable resource for studying the pharmacological and physiological control of EDS and cataplexy. Experiments using canine narcolepsy have demonstrated that increased cholinergic and decreased monoaminergic transmission are likely to be at the basis of the pathophysiology of the disorder. Pharmacological studies have shown that blockade of norepinephrine uptake mediates the anticataplectic effect of currently prescribed antidepressants, while blockade of dopamine uptake and/or stimulation of dopamine release mediates the awake-promoting effect of CNS stimulants. Studies in canine narcolepsy also suggest that mechanisms and brain sites for triggering cataplexy are not identical to those regulating REM sleep. It may thus be possible to develop new pharmacological compounds that specifically target abnormal symptoms in narcolepsy, but do not disturb physiological sleep/wake cycles. (See also postscript remarks).