Sleep in Disorders of Consciousness: A Brief Overview on a Still under Investigated Issue

Abstract

Consciousness is a multifaceted concept, involving both wakefulness, i.e., a condition of being alert that is regulated by the brainstem, and awareness, a subjective experience of any thoughts or perception or emotion. Recently, the European Academy of Neurology has published international guidelines for a better diagnosis of coma and other disorders of consciousness (DOC) through the investigation of sleep patterns, such as slow-wave and REM, and the study of the EEG using machine learning methods and artificial intelligence. The management of sleep disorders in DOC patients is an increasingly hot topic and deserves careful diagnosis, to allow for the most accurate prognosis and the best medical treatment possible. The aim of this review was to investigate the anatomo-physiological basis of the sleep/wake cycle, as well as the main sleep patterns and sleep disorders in patients with DOC. We found that the sleep characteristics in DOC patients are still controversial. DOC patients often present a theta/delta pattern, while epileptiform activity, as well as other sleep elements, have been reported as correlating with outcomes in patients with coma and DOC. The absence of spindles, as well as REM and K-complexes of NREM sleep, have been used as poor predictors for early awakening in DOC patients, especially in UWS patients. Therefore, sleep could be considered a marker of DOC recovery, and effective treatments for sleep disorders may either indirectly or directly favor recovery of consciousness.

Keywords: UWS and MCS; disorders of consciousness; sleep; wake-sleep cycle.

Figure 1

EEG pattern (on the left) and an 8 h recorded hypnogram (on the right) of normal sleep stages.

Figure 2

Structures and neurotransmitters responsible for arousal and sleep. In the figure: regulation of the ascending arousal system by the hypothalamic. Red lines represent the pathway of activation of the cortex, to enable the handling of inputs from the thalamus. The monoaminergic structures involved in this process are the locus coeruleus (LC), by noradrenaline (NA); the dorsal and median raphe nuclei, by serotonin (5-HT); the A10 cell group, by dopamine (DA); and the tuberomammillary nucleus (TMN), by histamine (His). Moreover, peptidergic structures are involved, such as the lateral hypothalamus (LHA), by orexin (ORX), or melanin-concentrating hormone (MCH) and basal forebrain (BF) neurons that contain γ-aminobutyric acid (GABA) or acetylcholine (Ach). The orange lane represents the input to the thalamus from cholinergic (ACh) structures, such as the upper pons, the pedunculopontine (PPT), and laterodorsal tegmental nuclei (LDT).