Narcolepsy: A Clinical Guide

AMAZING ADVANCES HAVE BEEN MADE IN OUR UNDERSTANDING OF THE PATHOPHYSIOLOGY AND TREATMENT OF NARCOLEPSY, AND MANY OF THOSE responsible for these advances have contributed to this book. By providing cutting edge basic science research information, this work is far more than “A Clinical Guide.” The integration of the basic science and clinical aspects of narcolepsy is nicely done, assuring relevance to both basic sleep scientists and clinicians interested in sleep in general, and narcolepsy in particular. The forward by Saper succinctly provides an overview of how far we have come, and gives glimpses of the future (gene therapy, cell transplants). The book is comprised of four sections: 1) Etiology, 2) Clinical Considerations, 3) Psychosocial Considerations, and 4) Management. Contributors to the Etiology section are pioneers in their respective areas. Mignot discusses genetic predisposition and pathophysiology with emphasis upon the dual influence of genetic and environmental factors. Sinton's animal model section underscores the importance of the canine and rodent models of narcolepsy, the latter of which have shown that the absence of orexin (hypocretin) signaling at both the 1 and 2 receptor are required to produce the most severe phenotype. Nofzinger discusses the neurobiological features of narcolepsy and cataplexy beginning to emerge from neuroimaging studies, and predicts that the increasingly sophisticated methods allowing for the quantification of numerous brain functions such as brain structure, metabolism, blood flow, and receptor binding will provide fascinating information on normal sleep and sleep in various disorders. The Clinical Considerations section is unique in that there is emphasis upon: 1) narcolepsy across the entire life cycle from early childhood to old age, 2) components of narcolepsy often not emphasized, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nocturnal sleep, and rapid eye movement sleep behavior disorder, and 3) the underlying causes of symptomatic narcolepsy. Misdiagnosis of narcolepsy is easily accomplished in the very young and very old. The Psychosocial Considerations section addresses important issues all too often neglected or glossed over in scientific discussions of narcolepsy. Even with aggressive medical management, for some patients with narcolepsy the symptoms may be poorly or incompletely controlled, leading to serious social and economic problems. This section is in essence a call for more studies in this area. The lack of a correct diagnosis of narcolepsy in children undoubtedly results in adverse academic and interpersonal consequences persisting into adulthood. The documented impairment in health related quality of life studies, educational and employment difficulties, and traffic safety issues should lead to standardized workplace accommodation and disability determination policies. The Management section reviews the older and newer treatments for narcolepsy. Much emphasis is placed upon modafinil, armodafinil, and gamma hydroxybutyrate (GHB) (sodium oxybate). The emphasis upon these newer drugs would have been more appropriate and more valuable were head-to-head comparisons with older agents available. The extraordinary cost of some of the newer medications is not acknowledged. As with all scientific advances, new knowledge leads to more questions and future directions. It is clear that there is a genetic component to narcolepsy—but the low concordance rate among identical twins (25%-31%) implicates an environmental factor, a leading candidate of which is an immune assault on hypothalamic hypocretin cells. Although isolated attempts at immune modification early in the course of narcolepsy have been disappointing, such treatments should be systematically studied. The well-documented psychosocial consequences of narcolepsy should lead to better management strategies which can be applied in the workplace—with particular reference to what constitutes “disability” in patients with narcolepsy and which workplace “accommodations” are practical and effective. Given the extraordinary cost of some currently available treatments for narcolepsy and cataplexy, head-to-head treatment studies with cost/benefit outcomes should be high priority. It is exciting to consider some of the emerging treatments for narcolepsy, such as: hypocretin-based treatment, hypocretin gene therapy, hypocretin cell transplants, stem cell transplants, and immune therapy. Overall, this book is far more than a clinical guide. It is unlikely that this much state-of-the-art information on all aspects of narcolepsy is available elsewhere. This book will be of great interest and value to basic scientists and clinicians alike. The list price is hefty.