Central Disorders of Hypersomnolence

PURPOSE OF REVIEW This article discusses the central disorders of hypersomnolence, a group of disorders resulting in pathologic daytime sleepiness, particularly narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, and Kleine-Levin syndrome. Disease features, diagnostic testing, epidemiology, pathophysiology, and treatment are reviewed.

RECENT FINDINGS Increasing evidence implicates autoimmunity in narcolepsy type 1, including a strong association with human leukocyte antigen–DQB1*06:02, association with a polymorphism in the T-cell receptor alpha locus in genome-wide association, and the identification of autoreactive T cells in patients with this type of narcolepsy. In contrast, the cause or causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Multiple treatment options exist, including two medications approved for the treatment of narcolepsy by the US Food and Drug Administration (FDA) in 2019. These include solriamfetol, a dopamine- and norepinephrine-reuptake inhibitor, and pitolisant, an H₃-inverse agonist/antagonist that increases histaminergic neurotransmission.

SUMMARY The central disorders of hypersomnolence all cause severe sleepiness but can be differentiated based on ancillary symptoms, diagnostic testing, and pathophysiology. It is important that these disorders are identified because multiple treatments are available to improve functioning and quality of life.

Address correspondence to Dr Lynn Marie Trotti, 12 Executive Park Dr, Atlanta, GA 30329, [email protected].

RELATIONSHIP DISCLOSURE: Dr Trotti has served on the editorial boards for Current Sleep Medicine Reports, Journal of Clinical Sleep Medicine, and Sleep and has received compensation/honoraria from the American Academy of Neurology, the American Academy of Sleep Medicine, Associated Professional Sleep Societies, the Kentucky Sleep Society, Medscape CME, Oakstone CME, and the Society of Behavioral Sleep Medicine and research/grant support from the American Academy of Sleep Medicine Foundation and the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NS083748, NS111280, and NS113912).

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Trotti discusses the unlabeled/ investigational use of antiepileptic medications (carbamazepine, phenobarbital, phenytoin, and valproate), lithium, clarithromycin, methylprednisolone, modafinil/armodafinil, pitolisant, sodium oxybate, solriamfetol, and traditional psychostimulants for the treatment of idiopathic hypersomnia or Kleine-Levin syndrome; antidepressants, lisdexamfetamine, and methamphetamine for the treatment of narcolepsy; and pitolisant for cataplexy.