A symposium entitled, “Idiopathic Hypersomnia: Past, Present and Future,” and co-chaired by Drs. Michel Billiard (Montpellier, France) and Sona Nevsimalova (Charles University, Prague, Czech Republic), took place at the World Association of Sleep Medicine (WASM) biannual conference in Valencia, Spain, on October 2, 2013.
Approximately 130 conference participants attended the meeting, which touched on many relevant topics.
Dr. Billiard presented a historical overview of the disorder and its terminology, noting that the modern-day introduction of the term, hypersomnia, originated with the Czech physician Bedrich Roth, whose seminal works—including his classic 1980 text Narcolepsy and Hypersomnia (S. Karger; NY, NY)—included a description of 620 personally observed cases, 167 of whom suffered from idiopathic hypersomnia as it has come to be known.
Karel Sonka (Czech Republic), a student of Dr. Roth, then presented an analysis of symptoms in 96 patients whom he had seen between 1999 and 2009 to identify which “cluster” of signs or symptoms was most useful in distinguishing between the entities of idiopathic hypersomnia with long sleep time (IH+LST), IH without long sleep time (IH-LST), narcolepsy without cataplexy, and classic narcolepsy with cataplexy. He suggested that the entities of IH+LST and narcolepsy with cataplexy are most distinct from one another, whereas IH-LST and narcolepsy without cataplexy are more similar than different and may best be considered together. He concluded that more specific signs or symptoms are or, even better, a biomarker is sorely needed to accurately distinguish among these entities.
This presentation was followed by Dr. Seiji Nishino (Stanford University), who shared what is known about the neurobiology and neurochemistry of these disorders. He reviewed the well-known causal relationship between hypocretin deficiency and narcolepsy with cataplexy and his own work, suggesting a deficiency in the wake-promoting chemical histamine as a potential common link to each of these disorders. He also reviewed more recent data at odds with his own work that leaves the field in search of a common final pathway that might account for sleepiness and points to promising new and alternative treatments. Dr. Nishino also reviewed the recent findings from Emory suggesting that an excess in intrinsic GABA systems may underlie sleepiness in the primary hypersomnias.
Dr. Nevsimalova’s followed with a presentation entitled, “The genetic aspects of idiopathic hypersomnia,” which expanded upon her original work with Dr. Roth, suggesting that the disorder often exhibits a familial pattern in 30% to 50% of cases, and that, in most instances, the disorder is transmitted in an autosomal-dominant pattern. Although she discussed a single paper suggesting that this might evolve from genes traditionally thought to control the body’s internal clock, she failed to touch on one larger study, which suggests that an allele in a gene involved in carnitine metabolism (first implicated in narcolepsy with cataplexy)—was similarly fingered in other hypersomnic disorders. It was a bit disturbing to see her summary slide that once again parroted the field’s long-held belief that idiopathic hypersomnia is a “very rare disease,” all the more distressing considering that her mentor and collaborator, Bedrich Roth, specifically noted in his textbook that it was not a rare disorder, equating its commonality to as great as that of multiple sclerosis and narcolepsy (with cataplexy)!
The symposium finished with an excellent summary by Dr. Timothy Morgenthaler (Mayo Clinic, Rochester, MN) relating to treatment. Dr. Morgenthaler singled out one recent Japanese study that highlighted the disorder’s negative impact upon quality of life. Importantly, he pointed out that the collective literature was sorely lacking—amounting to a cumulative 9 papers in the entire world’s literature. He touched on several studies that highlighted generally favorable treatment outcomes with modafinil and some of the traditional psychostimulants (eg, amphetamine derivatives) but noted that, in at least one third of cases, these therapies were ineffective and that therapy with multiple drugs was therefore often needed. Finally, Dr. Morgenthaler touched on the promising new findings from Emory suggesting the potential efficacy of both clarithromycin and flumazenil.
It was great to see IH get much needed attention at the meeting of the World Association of Sleep Medicine. That being said, the symposium really highlighted how much is unknown and the large gaps in knowledge that still exist. Clearly, there is a compelling need to effectively communicate that a large unmet clinical need exists, as even these experts often fell short of accurately conveying what we all feel at ground level: namely, that IH and its extended family (ie, many labeled as suffering from narcolepsy without cataplexy) is a fairly common disorder that consumes its victims and is very often refractory to available treatments. We are challenged by a lot of education and discovery science yet to complete. Let’s get it done!
This article was written for the Hypersomnia Foundation by Dr. David Rye.