廣瀬 真里奈

OBJECTIVES: We evaluated the continuity and effectiveness of oral appliances (OAs) for treating obstructive sleep apnea (OSA) in a psychiatric sleep clinic, specifically focusing on mild cases and those with psychiatric comorbidity. METHODS: We retrospectively examined the medical records of 106 OSA patients treated with OA. Survival analysis was performed to assess the discontinuation of OA use. Clinical Global Impression-Improvement (CGI-I) scale were obtained from medical records. The apnea-hypopnea index (AHI), measured by polysomnography (PSG), and Epworth Sleepiness Scale (ESS) were compared between diagnosis and after post-OA treatment if a second PSG for efficacy assessment was conducted. RESULTS: Among all 106 patients, Kaplan-Meier analysis estimated a discontinuation rate of 16.8% at 1 year. This tended to be higher for OSA patients with psychiatric comorbidity (22.7%) than those without (11.6%), though it was not statistically significant (P=0.08). The overall rate of improvement in CGI-I scale was 37.7% and was significantly lower in OSA patients with psychiatric comorbidity (25.0%) than those without (48.3%). Among the 74 patients who underwent a second PSG, AHI and ESS were significantly lower after OA treatment for the entire group and subgroups of OSA severity at diagnosis and psychiatric comorbidity, except for ESS in the moderate OSA severity subgroup. CONCLUSION: OA continuation was relatively good, and sleepiness was relieved by OA use, even in mild OSA patients and those with psychiatric comorbidity. However, the continuation and subjective improvement of symptoms were slightly lower in OSA patients with psychiatric comorbidity.

Delayed sleep phase disorder (DSPD) and mood disorders have a close relationship. However, the shared mechanisms by DSPD and mood disorders have not been well-elucidated. We previously found that micro-fluctuations in human behaviors are organized by robust statistical laws (behavioral organization), where the cumulative distributions of resting and active period durations take a power-law distribution form and a stretched exponential functional form, respectively. Further, we found that the scaling exponents of resting period distributions significantly decreased in major depressive disorder (MDD). In this study, we hypothesized that DSPD had similar characteristics of the altered behavioral organization to that of MDD. Locomotor activity data were acquired for more than 1 week from 17 patients with DSPD and 17 age- and gender-matched healthy participants using actigraphy. We analyzed the cumulative distributions of resting and active period durations in locomotor activity data and subsequently derived fitting parameters of those distributions. Similar to patients with MDD, we found that resting period distributions took a power-law form over the range of 2-100 min, with significantly lower values of scaling exponents γ in patients with DSPD compared with healthy participants. The shared alteration in γ suggests the existence of similar pathophysiology between DSPD and MDD.

BACKGROUND: The minimum narcolepsy criteria "mean sleep latency (MSL) ≤8 min and ≥2 sleep onset rapid eye movement (REM) periods (SOREMPs) on polysomnography (PSG) and the multiple sleep latency test (MSLT)," according to The International Classification of Sleep Disorders, Third Edition (ICSD-3), are not specific to narcolepsy. Recently, the characteristic sleep stage sequences preceding SOREMPs in narcolepsy have received attention, but their diagnostic utility remains unclear. METHODS: We retrospectively reviewed PSG/MSLT records and chart data for 102 Japanese patients with hypersomnia and at least one SOREMP. We examined the sporadic rates of two sleep stage sequences preceding the SOREMPs-wakefulness or stage 1 to REM (W/S1→R) and stage 2 to REM (S2→R)-comparing these between patient groups with narcolepsy type 1 (N = 28), narcolepsy type 2 (N = 19), and other hypersomnia (N = 55). We also examined the utility of three simple indices using the occurrence of W/S1→R SOREMPs for distinguishing between narcolepsy and other hypersomnia in patients who satisfied the minimum narcolepsy criteria. RESULTS: W/S1→R SOREMPs were significantly more frequent in narcolepsy than in other hypersomnia, and this tendency was also observed even in the patients who satisfied the minimum narcolepsy criteria. The three indices had moderate sensitivities and specificities for distinguishing between narcolepsy and other hypersomnia in patients satisfying the minimum narcolepsy criteria. CONCLUSIONS: The W/S1→R pattern was observed significantly more frequently in narcolepsy than in other hypersomnia, suggesting it may help with differentiating narcolepsy from other hypersomnia in patients demonstrating the narcolepsy criteria, although its ability to do so may be modest.

OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal and potentially violent behaviors during REM sleep, typically observed in older adult subjects. Previous reports have described a high risk for neurodegeneration in patients with iRBD; however, to date, no published study has analyzed an adequate number of Japanese patients. We retrospectively analyzed the incidence of neurodegenerative disorders among patients diagnosed with iRBD in our department. METHODS: The data were retrospectively collected from patients' medical records. The patients included in the study were diagnosed with iRBD using polysomnography in our department, from May 1, 2005 to November 30, 2018, with a follow-up of ≥6 months. Using the Kaplan-Meier (KM) method, we estimated the incidence of later diagnoses of neurodegenerative disorders among this cohort of patients with iRBD. RESULTS: Among 57 consecutive patients diagnosed with iRBD, 14 (24.6%) were later diagnosed with neurodegenerative disorders. Using the KM method, we estimated that the incidence was as high as 18.5% and 68.1% at 5 and 10 years, respectively. Of the 14 patients who developed neurodegenerative disorders, 12 (85.7%) had α-synucleinopathies (Parkinson's disease in eight patients, Lewy body dementia in three, Alzheimer's-type dementia in two, and multiple system atrophy in one). CONCLUSIONS: The results of this study suggest the high likelihood that iRBD may subsequently progress to neurodegenerative disorders in Japanese patients, a finding similar to those previously reported by studies performed overseas. Further studies using standardized prospective evaluation methods must be performed in Japan.

The objective of the study was to investigate the efficacy of ramelteon for insomnia, particularly with circadian disturbance, focusing on the relevance of dose and timing of administration. We reviewed the chart data of 145 continuous patients who received ramelteon for insomnia for the first time at the sleep clinic of the Department of Psychiatry, Fujita Health University Hospital (Aichi, Japan) between October 2010 and May 2014. Treatment efficacy was assessed using the Clinical Global Impression of Improvement (CGI-I) scale and this relationship with the dose and timing of administration was further analyzed. Symptoms in 56.6% of patients were improved (CGI-I ≦ 3). In a subgroup of 114 patients, especially aiming for phase advance, the ratio of improvement was 64.0%. The ratio of patients reporting symptom improvement tended to be great in the low-dose (1 or 2 mg) group and the low-dose + early administration (&gt 5 h before habitual bedtime) group, as compared with the remaining group however, this difference was not statistically significant. Significantly fewer cases in the low-dose group reported carry-over effects. In our specialized sleep clinic, there were many refractory cases of insomnia however, ramelteon was effective in about half of such patients. Particularly, ramelteon tended to be more effective for patients with insomnia and circadian disturbances, although differences among groups were not statistically significant. The effectiveness of the low-dose administration or the combination of low-dose and early-administration was equal or slightly better and acceptability tended to be better than other modes of administration.

We describe a case of parasomnia overlap disorder (POD) caused by paroxetine. Some reports have associated antidepressants such as selective serotonin reuptake inhibitors (SSRI) with rapid eye movement sleep behavior disorder. However, to the best of our knowledge, there have been no reports of POD caused by paroxetine. We diagnosed POD in a patient taking paroxetine using video-polysomnography (v-PSG) and then confirmed the improvement of POD symptoms by v-PSG after discontinuing the drug.

It has been recently discovered that blue wavelengths form the portion of the visible electromagnetic spectrum that most potently regulates circadian rhythm. We investigated the effect of blue light-blocking glasses in subjects with delayed sleep phase disorder (DSPD). This open-label trial was conducted over 4 consecutive weeks. The DSPD patients were instructed to wear blue light-blocking amber glasses from 21:00 p.m. to bedtime, every evening for 2 weeks. To ascertain the outcome of this intervention, we measured dim light melatonin onset (DLMO) and actigraphic sleep data at baseline and after the treatment. Nine consecutive DSPD patients participated in this study. Most subjects could complete the treatment with the exception of one patient who hoped for changing to drug therapy before the treatment was completed. The patients who used amber lens showed an advance of 78 min in DLMO value, although the change was not statistically significant (p = 0.145). Nevertheless, the sleep onset time measured by actigraph was advanced by 132 min after the treatment (p = 0.034). These data suggest that wearing amber lenses may be an effective and safe intervention for the patients with DSPD. These findings also warrant replication in a larger patient cohort with controlled observations.

Study Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia and elaborate motor activity in association with dream mentation. The melatonin receptor agonist ramelteon has been documented as being effective in two patients with secondary RBD. However, there are no reports on ramelteon treatment for idiopathic RBD. Methods: In an open-labeled trial, we treated 12 consecutive patients with idiopathic RBD for at least 4 w with 8 mg ramelteon given within 30 min before bedtime. Results: Ramelteon treatment did not have a clear effect on REM sleep without atonia or an RBD severity scale measured by video-supported polysomnography. However, clinical assessment using a visual analog scale showed a trend toward significance and there were also definitely positive changes in some individual cases. Ramelteon was well tolerated in most patients, with minor side effects. Conclusions: Considering that ramelteon is associated with few side effects, further study may ascertain whether patients with RBD could be effectively treated by ramelteon, especially when clonazepam may not be suitable due to its side effects.

Study Objectives: Patients with circadian rhythm sleep disorders (CRSDs) often have coincidence of orthostatic dysregulation (OD). Both disorders have many common clinical features. However, the prevalence of OD in patients with CRSD has not been examined. Methods: Thirty-eight patients with CRSD with either delayed sleep phase disorder or free-running disorder were tested for OD using the new orthostatic test, which was originally established by Tanaka et al. (< 20 years) and the Schellong test, i.e., the active standing test (>= 20 years). Results: The overall prevalence of OD in patients with CRSD was 57.9% (22/38), and prevalence of OD was 70% in patients under 20 years of age (14/20). These rates exceed the previously reported values in adolescents aged 14-15 years (15%), regarded as the age with highest OD prevalence. Prevalence was not significantly associated with CRSD severity and medications used. Conclusions: We observed a high prevalence of OD in patients with CRSD, suggesting some relationship between CRSD and OD. Large-scale case-control studies are warranted to investigate the underlying mechanisms for this comorbidity.

A sleep diary is often employed for diagnosing and treating hypersomnia. However, its reliability needs to be evaluated because overlooked chronic sleep insufficiency could be misdiagnosed as narcolepsy. In this study, we compared simultaneous sleep measurements using a sleep diary and by actigraphy in patients visiting our sleep clinic for the first time with complaints of excessive daytime sleepiness. Of the 28 patients enrolled, 24 complied with both these requirements. In this population, the results obtained using a sleep diary tended to estimate a statistically significant earlier sleep onset time and longer total sleep time than those via actigraphy. For total sleep time, this tendency was more prominent in patients with a higher Epworth Sleepiness Scale score. In 5 of the 24 (20.8%) patients, the sleep diary records indicated >6h of total sleep time while the actigraphy records indicated <6h of total sleep time, with a discrepancy of >1h. These results suggested that sleep insufficiency in hypersomnia patients may be overlooked when their sleep time is assessed using only a sleep diary in the initial phase of the diagnostic procedure, and the simultaneous use of actigraphy may be preferable in this assessment.