Multiple Sleep Latency Test/Maintenance of Wakefulness Test and Central Hypersomnias: Evolving Diagnostic and...

Central disorders of hypersomnolence include a spectrum of conditions, such as narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome, in which excessive daytime sleepiness is the primary feature. Subjective testing with tools, such as sleep logs and sleepiness scales, are often helpful in the evaluation of these disorders but do not necessarily correlate well with objective testing, such as polysomnography and multiple sleep latency test and maintenance of wakefulness test. The most recent International Classification of Sleep Disorders-Third Edition has incorporated biomarkers, such as cerebrospinal fluid hypocretin level, into the diagnostic criteria and have restructured the classification of conditions based on our evolved understanding of their underlying pathophysiologic mechanisms. Therapeutic approaches largely consist of behavioral therapy, with a focus on optimizing sleep hygiene, optimizing opportunity for sleep, and strategic napping, along with judicious use of analeptic and anticataleptic agents when necessary. Emerging therapy has revolved around hypocretin-replacement therapy, immunotherapy, and nonhypocretin agents, with the goal of better targeting the underlying pathophysiology of these disorders rather than addressing symptoms. The most novel treatments have targeted the histaminergic system (pitolisant), dopamine reuptake transmission (solriamfetol), and gamma-aminobutyric acid modulation (flumazenil and clarithromycin) to promote wakefulness. Continued research is required for a more solid understanding of the biology of these conditions to develop a more robust armamentarium of therapeutic options.