The "Known Unknowns" of Kleine-Levin Syndrome: A Review and Future Prospects

Kleine-Levin syndrome (KLS) is a rare, homogeneous, debilitating sleep disorder characterized by episodic hypersomnia, cognitive impairment, and behavioral changes. The etiology, pathophysiology, and optimal management of KLS remain uncertain. We identify the 5 key areas requiring urgent attention: KLS immunopathogenesis studies, next-generation genetics, multimodal functional imaging, biomarker discovery, and clinical drug trials. A centralized registry of afflicted individuals must be established. Disease uniformity should make the identification of associated genetic or imaging biomarkers easier, but clinical efforts require laboratory-based research to model the disease and generate preclinical data for clinical translation.