The Investigation of Sleepiness

Abnormal sleepiness is one of the primary symptoms of sleep disorders. Sleepiness is a normal physiologic phenomenon, however, and only becomes excessive when it occurs in situations when individuals can be reasonably expected to be awake and alert [1]. The degree of sleepiness depends on interplay between two factors: the time in the circadian cycle (process C), and the length of time from the last sleep period (process S) [2]. In subjects with normal circadian rhythmicity, sleepiness is maximal between 2 and 6 AM with a second minor peak 12 hours earlier in the afternoon. This rhythm is modified by the degree of accumulated sleep debt, a process that results in a homeostatic drive to induce sleep. Sleepiness is counterbalanced by alerting mechanisms, modulated predominantly by monoaminergic neuronal systems, such as dopaminergic and histaminergic pathways. The cluster of hypocretin (orexin) secreting neurons in the hypothalamus may be the master controller modulating monoaminergic systems, with projections from these neurons being widely distributed to the brainstem, diencephalon, and basal forebrain [3]. Sleepiness can be conceptualized as having two components: the subjective perception of the need to sleep, and the ability to transition from a state of wakefulness to a state of sleep [4]. The perception of the need to sleep is usually accompanied by objective manifestations, such as yawning, loss of neck extensor tone, pupillary constriction, ptosis, and a decreased attention span. The ability to fall asleep can be measured objectively using electroencephalographic activity and this forms the basis for the Multiple Sleep Latency Test (MSLT). The two components of sleepiness may dissociate; some patients with pathologic sleepiness have little or no warning of sleep onset, whereas patients with restless legs syndrome or psychophysiologic insomnia may have an intense desire to fall asleep but be unable to do so. Excessive sleepiness may be caused by factors that disrupt circadian rhythmicity, increase sleep debt by either voluntary curtailment of sleep time or fragmentation of sleep, or decrease the drive toward alertness [Box 1] [4]. Disorders of circadian rhythmicity include intrinsic disorders, such as delayed sleep phase syndrome, and extrinsic causes, such as the effects of shift work. Insufficient sleep syndrome, perhaps the commonest cause of excessive sleepiness, is caused by voluntary sleep curtailment. Fragmentation of sleep by diseases, such as obstructive sleep apnea syndrome, or environmental factors, such as exposure to a bed partner’s snoring [5], reduce the restorative value of sleep and increase sleep debt. Narcolepsy, in association with cataplexy, is caused by reduced activity of the wakefulness system secondary to decreased hypocretin production. Histamine receptor antagonists reduce alertness, as do benzodiazepine receptor agonists, such as benzodiazepines, barbiturates, and alcohol.