Symptomatic Narcolepsy or Hypersomnia, with and Without Orexin (Hypocretin) Deficiency

The symptoms of narcolepsy can occur during the course of other neurological conditions (i.e. symptomatic narcolepsy). We define symptomatic narcolepsy as cases that meet the International Sleep Disorders Narcolepsy Criteria, which are also associated with a significant underlying neurological disorder that accounts for excessive daytime sleepiness (EDS) and temporal associations. By 2005, we have counted 116 symptomatic cases of narcolepsy reported in the literature. As several authors previously reported, inherited disorders (n = 38), tumors (n = 33), and head trauma (n = 19) are the three most frequent causes for symptomatic narcolepsy. A review of these cases (especially those with brain tumors), illustrates a clear picture that the hypothalamus is most often involved. Reduced CSF orexin-A levels were seen in most symptomatic narcolepsy cases of EDS, with various etiologies including brain tumors, head trauma, and immune-mediated neurological conditions, such as neuromyelitis optica (NMO), and EDS in these cases is sometimes reversible with an improvement of the causative neurological disorder and an improvement of orexin status. It is also noted that some symptomatic EDS cases (with Parkinson diseases and the thalamic infarction) were observed,, but were not linked with orexin ligand deficiency. In this chapter, we first provide an overview of cases of symptomatic narcolepsy and EDS and then extend our discussions to the roles of the orexin system in EDS disorders associated with various neurological conditions.