Ask The Doctor: Idiopathic Hypersomnia vs Type 2 Narcolepsy

Question: Is there an overlap between idiopathic hypersomnia and type 2 narcolepsy?

Answer: The short answer to this question is yes. The only way to definitively distinguish idiopathic hypersomnia (IH) from type 2 narcolepsy (T2N) is the number of sleep-onset REM periods (SOREMPs) on diagnostic testing. However, in a group patients with IH, T2N, or symptoms of excessive sleepiness who had normal results on a single Multiple Sleep Latency Test (MSLT), researchers showed that the diagnosis changed more than half of the time when the MSLT was repeated¹—this means that some patients initially diagnosed with IH may later have a diagnosis of T2N, and vice versa, or they may have no sleep disorder diagnosed and then have T2N or IH on another MSLT, and, again, vice versa. In the general population as a whole (ie, not just those who are sleepy), the presence or absence of SOREMPs on repeated MSLTs is also quite variable,² suggesting that this may not be the best feature to use in discriminating among diseases. Indeed, prominent narcolepsy researchers have concluded that the presence of “2 or more sleep-onset REM periods [eg, on the MSLT] does not appear to have any specific pathognomonic significance.”³

The idea that T2N can overlap in some of its clinical symptoms with IH, as opposed to MSLT features (that is, “signs” of REM sleep on napping), was first proposed by the Czech sleep neurologist Bedrich Roth.⁴ In noting that many patients with T2N experienced long sleep periods and sleep inertia, he proposed that both IH and T2N might be considered as part of the same phenotypic spectrum or continuum of “disease.” Roth’s interpretation found further support in his recognition of a potential common heritability in these primary hypersomnias (that is, individuals with T2N and others with IH often have family members with the other condition).

Additional support for concluding that T2N and IH are more alike than they are different comes from four independent sources and lines of inquiry.

• First, nearly 20% of people with T2N sleep continuously for long periods (for example, for 11 out of 24 hours, thus, meeting the criteria for a diagnosis of IH).⁵
• Second, bioactivity that enhances the inhibitory function of GABA has been found in the cerebrospinal fluid (CSF) of many people with T2N and people with IH, whereas the same CSF samples exhibit normal levels of hypocretin.⁶
• Third, a substantial proportion of people with T2N and people with IH whose sleepiness/hypersomnia does not respond to traditional wake-promoting medications and whose CSF samples share an ability to excessively enhance GABA function respond positively to medications that are intended to suppress this enhancement (for example, flumazenil and clarithromycin).^6,7
• Fourth, results of a process called “cluster analysis” suggest that symptoms of IH (without long sleep time) and T2N are more similar than they are different.⁸ In cluster analysis, symptoms are compared among people while ignoring their official diagnosis, and new categories are created based on which symptoms or signs tend to occur together. In this study, three new “clusters” of disease were created:

  • People with T1N
  • People with IH with long sleep times (based on ICSD-2 criteria)
  • People with either T2N or IH without long sleep times

References

1          Trotti LM, Staab BA, Rye DB. Test-retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia. J Clin Sleep Med. 2013;9(8):789-795. PMID: 23946709.
2          Goldbart A, Peppard P, Finn L, et al. Narcolepsy and predictors of positive MSLTs in the Wisconsin Sleep Cohort. Sleep. 2014;37(6):1043-1051. PMID: 24882899.
3          Singh M, Drake CL, Roth T. The prevalence of multiple sleep-onset REM periods in a population-based sample. Sleep. 2006;29(7):890-895. PMID: 16895255.
4          Roth B. Narcolepsy & Hypersomnia. Basel, Switzerland: S. Karger Ag; 1981.
5          Vernet C, Arnulf I. Narcolepsy with long sleep time: a specific entity? Sleep. 2009;32(9):1229-1235. PMID: 19750928.
6         Trotti LM, Saini P, Koola C, LaBarbera V, Bliwise DL, Rye DB. Flumazenil for the treatment of refractory hypersomnolence: clinical experience with 153 patients. J Clin Sleep Med. 2016 [Epub ahead of print]. PMID:27568889.
7         Trotti LM, Saini P, Bliwise DL, Freeman AA, Jenkins A, Rye DB. Clarithromycin in gamma-aminobutyric acid-related hypersomnolence: a randomized crossover trial. Ann Neurol. 2015;78(3):454-65. PMID:26094838
8         Sonka K, Susta M, Billiard M. Narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time: a cluster analysis. Sleep Med. 2015;16(2):225-231. PMID: 25576137.