Motohiro Ozone

Re‐entrainment of circadian rhythm of plasma melatonin on an 8‐h eastward flight

To estimate the process of re‐entrainment we measured the melatonin rhythm on an eastward flight. After the baseline study, 24‐hour blood sampling of six male subjects was done on the first and fifth days. During the daytime the subjects were exposed to natural zeitgeber outdoors every day except the blood sampling day. They were analyzed with an illuminometer when under the bright light condition. Four of the six subjects showed orthodromic re‐entrainment, another subject showed antidromic re‐entrainment, and the other subject kept the baseline pattern of plasma melatonin. The rate of re‐entrainment in orthodromic re‐entrainment was about 55 min per day. Measuring the circadian rhythm of plasma melatonin has clarified the inter‐individual re‐entrainment difference.

Comparisons of short-term efficacy between individual and group cognitive behavioral therapy for primary insomnia

The purpose of this study was to compare the efficacy of individual and group cognitive behavioral therapy for insomnia (CBT-I) in outpatients with primary insomnia diagnosed by DSM-IV-TR. The participants were 20 individually treated (I-CBT-I) and 25 treated in a group therapy format (three to five patients per group) (G-CBT-I), which showed no significant difference regarding demographic variables between groups. The same components of CBT-I stimulus control therapy, sleep restriction therapy, cognitive therapy, and sleep hygiene education were applied on both groups. The shortterm outcome (4 weeks after treatment) was measured by sleep logs, actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and was compared between I-CBT-I and G-CBT-I. The results indicated that CBT-I was effective in improving subjective and objective sleep parameters and subjective sleep evaluations for both individual and group treatment. However, I-CBT-I resulted in significantly better improvements over G-CBT-I, in (i) objective and subjective sleep onset latency time, (ii) objective sleep efficacy and moving time during sleeping, (iii) overall sleep quality and duration of actual sleep time in PSQI, (iv) consequences of insomnia, control and predictability of sleep, sleep requirement expectation, and sleep-promoting practices in DBAS. The present study suggested the superiority of I-CBT-I over G-CBT-I in clinical settings, and further evaluations are necessary.

Mirtazapine improves visual hallucinations in Parkinson's disease: a case report

Psychotic symptoms often occur as a complication in Parkinsons disease patients, and a set of criteria for Parkinsons disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new‐generation antidepressants, mirtazapine. Mirtazapine improved the patients refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.

Clinical features of circadian rhythm sleep disorders in outpatients

The clinical data of 86 cases of primary circadian rhythm sleep disorder (primary CRSD) were retrospectively examined and compared to 40 cases of secondary circadian rhythm sleep disorder (secondary CRSD), who had presented with some kind of psychiatric or medical disorder, and had exhibited sleep‐wake rhythm disorders that were judged to be secondary CRSD based on sleep logs. The comparison of cases found that: (i) the mean age at first presentation to the clinic was significantly younger for primary CRSD compared to secondary CRSD; (ii) more secondary CRSD cases were unemployed than were Primary CRSD cases; (iii) more cases in the secondary CRSD group had a clear trigger for sleep‐wake rhythm disorder onset than cases in the primary CRSD group; and (iv) the types of sleep‐wake rhythm disorders in the primary CRSD group consisted of delayed sleep phase syndrome (DSPS), 72 (83.7%), non‐24 pattern, 11 (12.8%), and irregular, 3 (3.5%). In the secondary CRSD group there were 25 (62.5%) cases of DSPS pattern, 1 (2.5%) of non‐24 pattern and 14 (35.0%) with irregular pattern. The 56 (65.1%) cases with primary CRSD showed good response to vitamin B12 and bright light therapy; however, 28 (70.0%) cases with secondary CRSD did not respond to such therapies.

The effects of flumazenil on sleepiness, task performance and nocturnal sleep after anesthesia with midazolam.

The purpose of the present study was to clarify the changes in psychophysiological functions after anesthesia with midazolam (intravenous (i.v.) benzodiazepine anesthetic) and to examine the ability of flumazenil (benzodiazepine antagonist) to prevent the adverse effects of anesthesia with midazolam. Clinical dose of midazolam (0.1 mg/kg i.v.) was administered to seven healthy volunteers and either flumazenil (0.3 mg i.v.) or saline was injected at the end of the anesthesia. After anesthesia with midazolam, subjective sleepiness and euphoria increased significantly, but these changes were not observed when flumazenil was administered. In addition, sleep latency was prolonged and sleep efficiency decreased significantly after midazolam anesthesia with and without flumazenil. Slow wave sleep decreased significantly only by co‐administration of flumazenil.

The evaluation of hypnotics using Cyclic alternating pattern method

According to recent studies, it has been reported that Cyclic alternating pattern (CAP) method has high sensitivity to the changes in sleep structures and high correlations with daytime mood and psychophysiological functions in insomnia patients. Polysomnography technique has been demanded for developing novel hypnotics besides checking safety in clinical trials. Therefore, it is considered as one of the most appropriate PSG analysis method to evaluate hypnotics and the other sleep promoting drugs.

S26-6 CAP (cyclic alternating pattern) in psychiatric disorder

Periodic leg movements during sleep (PLMS) is frequently observed in rapid eye movement (REM) sleep behavior disorder (RBD) especially during REM sleep period. We made a series of studies for investigating the clinical significance and the underlying mechanism of PLMS in RBD. Consecutive 54 patients with idiopathic RBD without PLMS (iRBD w/o PLMS, 65.9±6.9 yrs), 27 patients with iRBD with PLMS (iRBD-PLMS, 67.7±7.1 yrs), and 31 patients with idiopathic PLMS (iPLMS, 63.5±5.9 yrs) were enrolled. Scores of Epworth Sleepiness Scale (ESS) were compared among the three patients groups. PLMS index, mean duration of PLMS, and inter-PLMS interval were calculated during both NREM sleep period and REM sleep period respectively, and compared among the three patient groups. Correlation analysis between ratio of PLMS related arousal index to PLMS index (PLMAI/PLMI) and proportion of REM sleep without atonia to total REM sleep (RWA/REM) were performed in the iRBD-PLMS group. The associated factor for the presence of PLMS during REM sleep period was also investigated in the subject iRBD group. In 15 out of iRBD-PLMS patients, effectiveness of the treatment with pramipexole, a dopamine agonst, was also evaluated. The iRBD-PLMS group showed significantly lower ESS score than the iPLMS w/o PLMS group did. PLMAI/PLMI was negatively correlated with RWA/REM. The iRBD-PLMS group showed significantly higher PLMS index, longer duration of PLMS, and shorter inter-PLMS interval than the iPLMS group did. RWA/REM appeared as a significantly associated factor for the presence of PLMS during REM sleep period among the iRBD patients. However, pramipexole treatment did not show a statistical decrease in the amount of PLMS. Conclusions: RWA could be associated with attenuation of arousal response to PLMS possibly leading to lower daytime sleepiness in iRBD. Our result impresses that PLMS during this sleep period could become an disease process marker of iRBD.

55. New sleep electroencephalogram analysis, CAP (Cyclic Alternating Pattern) method for sleep study and clinical use

A 20-year-old woman has suffered from myalgia and involuntary movements in the lower extremities since age 10. Her developmental history was normal and the family history was non-contributory. On examination, myokymia-fasciculation was observed in the lower extremities and worsened by exercise and exposure to cold, however, other neurological examination was unremarkable. The blood tests were unremarkable including negative antibody against voltage-gated potassium channel (VGKC). The tibial F study showed prolonged afterpotential after the appearance of the F waves. Needle EMG showed fasciculation potentials and doublets–triplets in the lower extremities. Threshold tracking demonstrated the following abnormalities: (1) recovery cycle showing complete lack of late subexcitability, (2) depolarizing threshold electrotonus showing lack of accommodation (S2), (3) the remarkably decreased strength-dependent time constant. These recording was similar to the ones recorded in rats by applying the selective KCNQ channel blockers XE991 (Schwarz et al., 2006). We concluded that slow potassium channel dysfunction caused axonal hyperexcitability demonstrating fasciculation-myokymia. Thus, threshold tracking is useful in identifying channelopathy in a non-invasive manner.

Preliminary evaluation of cyclic alternating pattern (CAP) in Japanese insomniac patients

recorded before lights out until the termination of the first REM sleep in 14 young healthy subjects. The subject remained in a semirecumbent posture in dim light during waking period before light out. The effects of circadian rhythm were controlled. Heart rate variability was calculated using the MemCalc method from electrocardiogram R–R intervals. The heart rate variability was analyzed in time course changes before and after sleep onset. The LF/(LF+HF) and LF/HF declined clearly prior 30 min to sleep onset. The HF increased prior to sleep onset in consecutive phases. The change of LF/(LF+HF) and LF/HF preceded slow wave sleep and REM sleep. There was no clear stage dependency after sleep onset in HF. The results mentioned above suggest that the cardiac sympathetic nervous activity represented LF/ (LF+HF) and LF/HF may possibly anticipate sleep and each sleep stage onset.

Sleep Facilitating Effects of Vitamin B12

Recent experiments (Kamgar-Paris 1983, Okawa 1990) have shown that vitamin B12 (Vit. B12) has therapeutic effects on circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24 hours sleep wake rhythm disorder (Non-24). Regarding the mechanisms of therapeutic action of Vit. B12 on circadian rhythms sleep wake disorders, many study consider its effects on the phase or period of circadian rhythms and on photo sensitivity. But at the present time the definite mechanisms of action are still unclear.