You are only coming through in waves: wakefulness variability and assessment in patients with impaired consciousness

The vegetative state (VS) is defined as a condition of wakefulness without awareness. Being awake and being asleep are two behavioral and physiological manifestations of the daily cycles of vigilance and metabolism. International guidelines for the diagnosis of VS propose that a patient fulfills criteria for wakefulness if he/she exhibits cycles of eye closure and eye opening giving the impression of a preserved sleep-wake cycle. We argue that these criteria are insufficient and we suggest guidelines to address wakefulness in a more comprehensive manner in this complex and heterogeneous group of patients. Four factors underlying wakefulness, as well as their interactions, are considered: arousal/responsiveness, circadian rhythms, sleep cycle, and homeostasis. The first refers to the arousability and capacity to, consciously or not, respond to external stimuli. The second deals with the circadian clock as a synchronizer of physiological functions to environmental cyclic changes. The third evaluates general sleep patterns, while homeostasis refers to the capacity of the body to regulate its internal state and maintain a stable condition. We present examples of reflex responses, activity rhythms, and electroencephalographic (EEG) measurements from patients with disorders of consciousness (DOC) to illustrate these factors of wakefulness. If properly assessed, they would help in the evaluation of consciousness by informing when and in which context the patient is likely to exhibit maximal responsiveness. This evaluation has the potential to improve diagnosis and treatment and may also add prognostic value to the multimodal assessment in DOC.