A Year in Review—Basic Science, Narcolepsy, and Sleep in Neurologic Diseases

Abstract

THE PAST YEAR HAS BEEN VERY FRUITFUL FOR SLEEP IN THIS BROAD AND DIVERSE AREA OF RESEARCH. As expected from recent progress in this area, a total of 12 original papers have been published in the area of narcolepsy, ranging from descriptions of the psychological and socioeconomic impact of the disease to new treatments. Following on the pioneer work of Broughton and others1,2 who showed that narcolepsy had socioeconomic costs similar to those of depression or epilepsy, Dodel et al3 studied the monetary cost to German society of narcolepsy evaluation and treatment and of a narcolepsy disability program. Total annual costs amounted to approximately $12,000 per year, mostly as a result of early retirement. Interestingly, in this population of 75 patients, a significant amount of the cost was due to the appearance of newer more expensive treatments such as modafinil. It is suspected that a similar increase in cost is also occurring in the United States with the recent change in treatment strategies that involve newer drugs such as modafinil, sodium oxybate, and novel antidepressants. The same authors also reported a study assessing attention deficits in narcoleptic patients.4 Surprisingly, they found attention deficits that are difficult to explain solely by sleepiness, suggesting neurobiologic abnormalities in systems other than sleep regulation in hypocretin-deficient patients. In addition to attention deficits, it has also been reported that narcoleptic patients exhibit attenuated emotion-information processing.5 Several articles are also increasing our understanding of the pathophysiology of narcolepsy—either in the context of isolated primary narcolepsy or as a result of a secondary etiology. The study of the hypocretin system in narcolepsy cases was discussed by Kubota et al,6 Martinez-Rodriguez et al,7 and Vankova et al.8 The Kubota et al article6 was remarkable in that patients very close to disease onset were found to have low hypocretin-1 levels in the cerebrospinal fluid, emphasizing the use of the cerebrospinal fluid test for early diagnosis.9 The other 2 articles documented the presence of hypocretin abnormalities in some cases of excessive daytime sleepiness in association with myotonic dystrophy 7 but not in cases of narcolepsy secondary to NiemannPick disease, Type C. 8 The association of narcolepsy-like sleepiness in myotonic dystrophy is interesting, as the disorder is frequently associated with sleep apnea, potentially confusing the issue of what causes the sleepiness. A similar association of primary excessive daytime sleepiness, hypocretin abnormality, and sleep-disordered breathing has been reported in some cases of Prader-Willi syndrome.9 Clinically, these associations emphasize the importance of considering narcolepsy even if sleep apnea is present because a significant portion of narcoleptic patients develops obesity and has associated sleep apnea. DominguezOrtega et al,10 for example, recently reported a patient with Down syndrome and narcolepsy-cataplexy. Because Down syndrome is commonly associated with sleep apnea,11 this case again emphasized that it is critical to ask about cataplexy and narcolepsy symptoms in all patients with sleepiness. In the area of isolated narcolepsy, the report by Dauvilliers et al12 that narcoleptic patients are more often born in March and less often born in September is notable. Similar findings have been reported in Germany,13 raising the possibility that prenatal or early postnatal environmental influences may influence the subsequent development of the disorder. A possible explanation for these phenomena may involve the shaping of the immune system of the fetus during pregnancy or immediately after birth. The finding that narcolepsy is associated with a hypocretin cell loss led Overeem et al14 to examine whether structural changes in the hypothalamus can be identified in patients with narcolepsy using voxel-based morphometric study of the brain. This area is of great interest because, if successful, it could lead, on a long-term basis, to the development of diagnostic imaging procedures for narcolepsy. Unfortunately, however, no changes were observed, suggesting that the lesion may be too small to be detectable by conventional imaging techniques. Other authors have reported changes in various brain areas using the same technique, raising the possibility that a refinement of the technique may be successful in detecting an abnormality.15,16