Yasuro Takahashi

Predisposing factors in delayed sleep phase syndrome.

We classified 64 patients with chronic delayed sleep phase syndrome (DSPS) into the primary (n = 53) and secondary (n = 11) group according to presence or absence of such signs as difficulty in waking up which appeared much earlier than the onset of DSPS. The age at the onset of the early signs concentrated in adolescence. The familial occurrence of DSPS was noted in 11 patients of the primary group. In human leukocyte antigen (HLA) typing, the incidence of DR1 positivity alone was significantly higher in DSPS patients than in healthy subjects. Minnesota Multiphasic Personality Inventory revealed high scores on depression, psychoasthenia and hypochondriasis. We suggest that a predisposition to DSPS includes biological, genetic, social and psychological factors, various combinations of which may lead to DSPS.

Possible association of human leucocyte antigen DR1 with delayed sleep phase syndrome

The study investigated the human leucocyte antigen (HLA), types A, B and DR, of 42 patients with delayed sleep phase syndrome (DSPS) and compared the frequencies of the antigens with those in 117 healthy controls. The comparison revealed that the gene frequencies and positivities of HLA‐A, ‐B and ‐DR, except for DR1, had no significant differences between the patients and controls. The frequency of HLA‐DR1 was increased in the DSPS patients as compared with that in the healthy controls (P = 0.0069 in positivity). Although the corrected P‐value (0.069) for multiple comparisons almost reached the significance level, the results indicated a possible association of the HLA‐DR1 antigen with DSPS. This study suggests that there are genetic predispositions to DSPS.

Subjective sleep quality and suggested immobilization test in restless leg syndrome and periodic limb movement disorder

Abstract The severity of restless leg syndrome (RLS) and/or periodic limb movement disorder (PLMD) was investigated by using a suggested immobilization test (SIT) and by measuring the influence of these disorders on the subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI). Patients with RLS and those with both RLS and PLMD showed remarkably high values for PSQI and SIT, whereas patients with PLMD only showed normal values for PSQI. These findings suggest that there is only a small pathological significance for periodic limb movements, and demonstrate the efficacy of SIT and PSQI for evaluating the severity of these disorders.

Clinical significance of sleep‐related breathing disorder in narcolepsy

Abstract Both the influence of comorbid obstructive sleep apnea–hypopnea syndrome (OSAHS) on daytime sleepiness and its pathological mechanism in 10 narcoleptic patients was studied. Mild elevation of esophageal negative pressure and obstruction in the velopharyngeal area, as observed by upper airway magnetic resonance imaging, during apneic episodes was observed in the subjects. Severity of the disorder was correlated positively with body mass index, and the latencies of the multiple sleep latency tests were not improved with nasal continuous positive airway pressure treatment in subjects. Pathogenesis of OSAHS in narcolepsy was thought to be almost similar to typical OSAHS, and that the disorder seemed to lack a pathological influence on daytime sleepiness.

Alpha-delta sleep in a case with non-24 h sleep-wake syndrome: Quantitative electroencephalogram analysis of alpha and delta band waves

Abstractu2002 Four all‐night polysomnograms of a 39‐year‐old male patient with non‐24 h sleep‐wake syndrome were recorded. We analysed electroencephalograms (EEG) with the power spectrum method and the wave pattern recognition analysis of Fujimori. The EEC of the rest waking condition showed normal patterns. High‐voltage diffuse alpha band waves were observed in sleep stages 2, 3 and 4. The integrated area of the alpha band waves in the analysis epochs showed a strong positive correlation to the delta hand components in the power spectrum of the same epoch during sleep (correlation coefficients r= 0.762–0.815). Alpha hand waves during sleep were clearly different from the alpha waves in the rest waking condition, with respect to slower peak frequency and the frontal dominant voltage distribution.

Rat circadian rhythms entrain to a descending saw-tooth light intensity cycle

We reexamined whether rat circadian rhythms entrained to the light intensity cycle of a descending saw-tooth (ST-d) form, in which illuminance decreased rectilinearly from 300 lx to 0 lx in 24 h, and abruptly returned to 300 lx (lights-on time). Ambulation, drinking and subcutaneous body temperature were simultaneously monitored in 5 intact, 5 pinealectomized and 5 orchiectomized rats. Additionally, sleep was monitored in the intact rats. In all the rats, entrainment was confirmed during 65 days exposure to the ST-d cycle. The waveforms of the entrained rhythms were much modified compared with those during LD 12:12. The estimated activity periods of the entrained rhythms straddled the lights-on time of the ST-d cycle. In all the groups of rats, administration of a single ST-d cycle in constant dim red light produced only delay shifts irrespective of its circadian phase, and there was no significant circadian variation in the magnitude of phase shifts. The results indicate that rat circadian rhythms entrain to the ST-d cycle with an unexpected phase position, which cannot be explained by the phase-response curve.

The lower entrainable limit of rat circadian rhythm to sinusoidal light intensity cycles: A preliminary study

The lower entrainable limit of the circadian behavioral rhythm was examined in rats exposed to sinusoidal light intensity cycles with maximum illuminance of 20 lux and the minimum of 0.01 lux. The period (T) of the light intensity cycle was initially kept at 23.5 h for 20 cycles, and then shortened to 23 h for 33 cycles. Thereafter the rats were released into constant darkness. Five out of 10 rats entrained their circadian rhythms to T = 23.5‐h cycle, and they also entrained to the T = 23‐h cycle. The phase angle of entrainment was almost unchanged when T was shortened from 23.5 h to 23 h. These results suggest that the T = 23‐h cycle was close to the lower limit of entrainment.

Effect of Vitamin B12 (Mecobalamin) on the Free‐Running Period of Rat Circadian Behavioral Rhythm

The oral administration of vitamin B,, (VB,,) has been reported to entrain a freerunning circadian rhythm in patients with non-24 hour sleep-wake syndrome to the 24hour (hr ) socio-environmental cycle. Although the chronobiological action of VB,, has so far not been known, VB,, may bring the intrinsic period of circadian rhythm close to 24 hr and/or may improve the perception of Zeitgebers by the circadian system. The aim of the present study is to examine the effect of mecobalamin (methylcobalamin) on the free-running period ( 7 ) of circadian behavioral rhythm under constant conditions in Sprague-Dawley male rats. Mecobalamin is an active form of VB,, present in the body. Since it is converted into hydroxocobalamin by light, great care was taken to protect the mecobalamin-containing material from light exposure during the experiment. A comparison of T was made between serum low and high VB,, states. The serum low VB,, state was made by feeding rats with a completely VB,,-deficient chow [B,,(-) chow]. The serum high VB,, state was produced by feeding with the chow containing 1 mg of mecobalamin per kg [BIZ( +) chow] or by subcutaneous VB,, infusion. After 1 ml of blood was collected by tail incision, the serum total VB,, concentration ( a ) and serum unsaturated VB,,-binding capacity ( b ) were determined by a competitive protein-binding assay and il radioassay with dextran-coated charcoal, respectively. The serum VB,, bound-saturated rate was calculated by a / ( a + b ) . 7 was determined by chi-square periodogram.

Tongue position controller as an alternative treatment for obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common, but underdiagnosed, public health problem that predisposes the patient to higher cardiovascular morbidity and mortality. Nasal continuous positive airway pressure (nCPAP) has been established as a standard treatment for OSA for nearly three decades, whereas oral appliances (i.e., mandibular repositioning splint and tongue retaining device) have been prescribed for patients with mild to moderate OSA and/or who have failed to respond to nCPAP [1–3]. A tongue retaining device is particularly recommended in patients who are contraindicated for mandibular repositioning splints due to an insufficient number of teeth, severe periodontal disease, temporomandibular joint problems, and so on [1]. To improve the patency of the pharyngeal airway, this device holds the tongue at a protruded position by negative pressure that is generated within the anterior socket, thus possibly displacing the tongue base ventrally. Dort and Brant [4] succeeded in reducing the respiratory disturbance index (from a baseline of 15.5±17.6 to 8.9±7.6 at follow-up) with a tongue retaining device that had an improved anterior socket for tongue suction. There have also been a few reports on the efficacy of, compliance with, and indications for a tongue stabilizing device [5–7], which is considered to be a type of tongue retaining device. In a pilot study, Kingshott et al. [5] first documented that a tongue stabilizing device reduced the severity of snoring and microarousals. Deane et al. [6] later demonstrated that a tongue stabilizing device was as efficacious as a mandibular repositioning splint in terms of reducing the apnea– hypopnea index (AHI), but noted that a lower compliance was observed with the tongue stabilizing device when both appliances were offered. After the Fukushima Daiichi Nuclear Power Plant accident that occurred right after the East Japan earthquake, Tsuiki et al. [7] proposed that a tongue stabilizing device could be a first-line treatment modality for snorers with suspected OSA at temporary refuges because of its simplicity. Although these reports describe certain favorable results with tongue retaining devices, strong evidence indicating the effectiveness of the device is still limited. Clinically, incomplete tongue suction often fails to hold the tongue, leading to unsatisfactory outcomes. Moreover, the tongue retaining device does not involve alternative methods when the suction pressure is incomplete. This may result in an overall lower effectiveness of tongue retaining devices [2] in comparison with mandibular repositioning splints. S. Tsuiki :K. Maeda :M. Kobayashi : T. Sasai :Y. Takahashi : Y. Inoue Neuropsychiatric Research Institute, Tokyo, Japan

Clinical significance of cataplexy and HLADR1501 in narcolepsy

Clinical symptoms and multiple sleep latency test (MSLT) measures among narcoleptic patients with both cataplexy and HLADR1501 were compared with cataplexy‐free narcoleptic patients with a positive finding of HLADR1501 and cataplexy‐free patients without HLADR1501. Both mean sleep onset latencies and rapid eye movement (REM) latencies on MSLT were shorter in the patients with cataplexy compared with the cataplexy‐free patients. In four cataplexy‐free patients without HLADR1501, nocturnal sleep was remarkably long and their excessive daytime sleepiness did not respond to treatment. The findings suggest that the severity and disease mechanism of narcolepsy might become heterogenous when cataplexy and HLADR1501 are considered.