Unraveling Narcolepsy: A PRISMA-Compliant Systematic Review on Definitions, Epidemiology, Pathophysiology, and Future Perspectives

Abstract

Introduction: Narcolepsy is a chronic neurological disorder affecting millions of individuals worldwide, characterized by excessive daytime sleepiness, cataplexy, and other debilitating symptoms. Despite recent advances in the understanding of its etiology and treatment, significant diagnostic and therapeutic challenges remain. This systematic review aims to provide a comprehensive and critical overview of the current evidence on narcolepsy, encompassing its definition, classification, epidemiology, pathophysiology, diagnosis, treatment, and future perspectives.
Methods: A systematic search was conducted in the PubMed, Scopus, and Google Scholar databases using key terms such as narcolepsy, diagnosis, pathophysiology, and treatment. Initially, 56 publications were identified, of which 48 met the inclusion criteria after removing duplicates and applying exclusion criteria. The selection process followed the PRISMA statement.
Results: Narcolepsy type 1 is characterized by the selective loss of 85-95% of orexin-producing neurons in the lateral hypothalamus, mediated by an autoimmune mechanism in individuals carrying the HLA-DQB1*06:02 allele. Global prevalence ranges from 25 to 50 cases per 100,000 individuals, with significant geographical variations. Diagnosis is based on polysomnography, the multiple sleep latency test, and measurement of hypocretin-1 in cerebrospinal fluid. Treatment includes modafinil, sodium oxybate, and pitolisant, while orexin receptor agonists represent a promising future therapy.
Conclusions: Narcolepsy is an autoimmune neurodegenerative disorder with significant systemic impact. Early diagnosis and multidisciplinary management substantially improve patient prognosis and quality of life. Future research focuses on therapies targeting the underlying cause and on diagnostic tools based on artificial intelligence.