Klein T, Martens H, Dijk D J, Kronauer R E, Seely E W, Czeisler C A
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02138.
Sleep. 1993 Jun;16(4):333-43. doi: 10.1093/sleep/16.4.333.
Sleep disturbances and the failure to entrain circadian rhythms to the 24-hour day have been reported in the majority of totally blind subjects. The present case study of a totally blind man with a well-documented recurring sleep disturbance was designed to investigate the mutual relationship between sleep and the circadian timing system. The 63-year-old subject, a high school teacher with a regular work schedule, had suffered from cyclically recurring insomnia for the past 28 years. Analysis of a sleep log that he had kept for the past 15 years suggested that his circadian rhythms were not entrained to the 24-hour day. During a 3-month inpatient study, the period of the endogenous circadian pacemaker was assessed by analysis of ambulatory core body temperature, urinary excretion and a series of estimates of the phase of core body temperature cycles and plasma cortisol levels during constant routines. All circadian markers revealed periods in the range of 24.22-24.27 hours, with no evidence for a modulation of the observed periods by the sleep-wake cycle. During this 3-month inpatient study, a complete cycle of the subject's sleep disturbance and remission was polysomnographically documented while the subject lived on a regular 24-hour schedule. Because the subject's circadian rhythms were free-running and his sleep times were fixed, sleep occurred at virtually all circadian phases. Analysis of sleep latency, REM sleep latency, sleep duration, wake in sleep episode and REM sleep during sleep episode revealed a strong modulation by circadian phase. These findings in this blind man suggest that: 1) the period of his cyclically recurring sleep disturbance is directly related to the nonentrained period of an endogenous circadian pacemaker that drives circadian variation in core body temperature, urinary excretion, plasma cortisol and sleep propensity; 2) both his sleep structure and the severity of his daily sleep disruption are directly related to circadian phase and 3) his circadian pacemaker, which has an endogenous period that deviates only 0.2-0.3 hours from 24 hours, cannot be entrained by periodic daily exposure to nonphotic time cues, including a very regular 24-hour sleep-wake schedule.
大多数全盲受试者都存在睡眠障碍，且其昼夜节律无法与24小时的一天同步。本案例研究针对一名有充分记录的反复出现睡眠障碍的全盲男性，旨在研究睡眠与昼夜节律计时系统之间的相互关系。该63岁受试者是一名高中教师，工作时间规律，在过去28年中一直患有周期性反复失眠。对他过去15年所记睡眠日志的分析表明，他的昼夜节律并未与24小时的一天同步。在为期3个月的住院研究中，通过分析动态核心体温、尿排泄以及在固定程序期间对核心体温周期和血浆皮质醇水平相位的一系列估计，对内源性昼夜节律起搏器的周期进行了评估。所有昼夜节律指标显示周期在24.22 - 24.27小时范围内，没有证据表明观察到的周期受睡眠 - 觉醒周期调节。在这3个月的住院研究期间，当受试者按照规律的24小时作息时间表生活时，其睡眠障碍和缓解的完整周期通过多导睡眠图进行了记录。由于受试者的昼夜节律是自由运行的，且睡眠时间固定，睡眠几乎出现在所有昼夜节律阶段。对睡眠潜伏期、快速眼动睡眠潜伏期、睡眠时间、睡眠中觉醒发作以及睡眠发作期间的快速眼动睡眠的分析显示，其受昼夜节律相位的强烈调节。这位盲人的这些发现表明：1）他周期性反复出现的睡眠障碍周期与驱动核心体温、尿排泄、血浆皮质醇和睡眠倾向昼夜变化的内源性昼夜节律起搏器的非同步周期直接相关；2）他的睡眠结构和日常睡眠中断的严重程度均与昼夜节律相位直接相关；3）他的昼夜节律起搏器，其内源周期仅比24小时偏离0.2 - 0.3小时，无法通过每日定期暴露于非光时间线索（包括非常规律的24小时睡眠 - 觉醒时间表）而被同步。
