A ReLACSing Blog #17: Does Idiopathic Hypersomnia Exist?

Maybe.

And you thought I would say “unlikely”! (I will say “unlike,” just to keep you somewhat happy then). Unlike the named conditions narcolepsy type 2 (NT2) and periodic limb movement disorder (PLMD) discussed in previous blogs, the one with the term “idiopathic” in the name may actually be the only one of the three with possible existence. Unfortunately, like in NT2, the diagnosis of this condition is largely based on a highly flawed test, the multiple sleep latency test (MSLT), so if the condition does exist, the majority diagnosed with the condition don’t have it.

Unlike in NT2, in which the diagnosis is essentially made from symptoms of excessive sleepiness and specific MSLT results, there may be some more classic symptoms of IH, one version of which used to be called idiopathic hypersomnia with long sleep times. In a “classic” case, a person with this description sleeps an excessive amount on a daily basis, upwards of 9+ per day (abnormally long for an adult) and has a signature feeling of sleep inertia, sleep drunkenness, when woken up from sleep. Sleep inertia is like getting woken up feeling like you were hit by a truck. You feel sleepy, your reaction time is slowed, and your thinking is impaired. The feeling may overlap with the alcohol-related drunkenness with which some are familiar, so sleep drunkenness does have its merits for terminology. Sleep inertia describes the feeling that you woke up from sleep, but your brain’s sleep still has the inertia carrying its sleep into your wake. (OR, it is the feeling of the inertia from a large semi-truck screaming down the highway when it hits you to wake you up.) The sleep inertia also occurs during short naps as well. Healthy individuals and even those with narcolepsy type 1 (the form of narcolepsy that has been well-characterized based on the biology and clinical symptoms, aka narcolepsy with cataplexy) may feel refreshed after a short nap, but not this group.

Photo by Robson Hatsukami Morgan on Unsplash

Sleep inertia feels like you got woken up at night, hit by one of these.

In addition to long sleep times and sleep inertia, the individual has an easy ability to fall asleep quickly during the day despite getting all that sleep. However, as we have discussed previously, falling asleep quickly can be due to any number of common factors (sleep deprivation, poor sleep hygiene, sleep apnea, irregular sleep-wake cycles, medications that cause drowsiness, etc.) rather than a rare, idiopathic sleep condition. On an overnight sleep study (polysomnogram/PSG), patients with classic IH have a high sleep efficiency, meaning they are asleep for a high percentage of the time they are in bed, often >90% of the time is spent objectively asleep. 

Now let’s go to the diagnosis of idiopathic hypersomnia, based on the criteria from the 3rd edition of the International Classification of Sleep Disorders (ICSD-3). The diagnostic criteria includes (to summarize): a person with a strong need to sleep (excessive sleepiness), no cataplexy, and either of the following two (a or b): (a) test results on the MSLT that show an average time to fall asleep of 8 minutes or less; or (b) a total of 660+ minutes of sleep in a 24 hour period with sleep testing (PSG) or by wrist actigraphy averaged over the previous seven days. As a reminder, wrist actigraphy is similar to how commercially available sleep trackers like the Oura ring or Apple Watch estimate sleep, largely by movement of the body. Also, as a reminder, actigraphy is, inexplicably, rarely covered by insurance, so many sleep centers don’t do it, when it is probably the best test in the evaluation of IH and most patients with excessive daytime sleepiness.

The last parts of the diagnosis are again the ones often glossed over by medical professionals. A physician should exclude insufficient sleep, inconsistent sleep patterns, and other common causes of daytime sleepiness. This should be done initially at the clinic appointment with the patient who is reporting excessive sleepiness or amount of daily sleep. Unfortunately, many physicians do not have enough time during the appointment to assess sufficiently a day-by-day and week-by-week breakdown of their sleep pattern, schedule, and habits. Ideally, this is done before a sleep study is ever ordered. If somehow the patient is sleeping very consistently, but with rather long sleep times, demonstrates good sleep hygiene, and has no risk of the myriad other sleep-affecting circumstances, only then should the clinician consider the PSG-MSLT. These two tests absolutely should be preceded by two weeks of actigraphy, which will more objectively assess the actual sleep pattern and amount of sleep.

I cannot tell you how many patients in my career were on the verge of progressing down this IH pathway or were already misidentified with IH with an obvious cause that was not assessed. So many were not getting enough sleep or had a physiologically inappropriate sleep pattern prior to the sleep testing that unfortunately led to dubious and misleading results. A classic case was a college student who reported 8+ hours of sleep with a consistent schedule but was still dozing off in the lecture hall during class (I don’t think I’ve been out of school that long, but do they still have lectures in lecture halls any more? Gosh, is everything through video now? Heck, I don’t even think ReLACS Health sees people in person either, what’s going on with technology these days?!). The sleep medicine fellow I was supervising was considering an investigation for IH, and I told him before I would allow the MSLT, he would have to do actigraphy and that would give the fellow the non-idiopathic cause of the symptoms. Sure enough, in a 19 year-old who needs about 8-9 hours of sleep per night, the actigraphy showed an average of LESS than 6 hours of sleep for a week! And he knew we were monitoring him! He had two nights with less than 4 hours of sleep. Keep in mind, getting less than the 4-hour threshold alone, much less with other nights of deprivation, causes a similar level of impairment as the legal limit for blood alcohol content. He had a few nights in which he was up until 4 am but had 9 am classes. In a college student, this is not surprising at all. Had we not done the actigraphy and just run the PSG-MSLT combo, he would have slept 10 hours at 95% efficiency and fallen asleep in 4 minutes on average on the MSLT. He would have carried the diagnosis of idiopathic hypersomnia for years, possibly being subjected to unnecessary and potentially risky treatments like amphetamines and other stimulants. 

OK, so for the rare subset of these individuals who do pass through a thorough vetting process to exclude other causes, what is the cause then? Drs. Lynne Marie Trotti, David Rye, and colleagues at Emory did some nifty spinal fluid analysis and found that there may be overactivity of the GABA-A receptors in the brain that cause the condition in a subset of patients. GABA is a neurotransmitter, or chemical that brain cells use to communicate. I liken GABA to the brakes on the entire engine of the brain, it just slows everything down. They have proposed that if GABA is overactive or turns on too much during the day, this would make one sleep for excessive amounts of time, fall asleep fast, feel sleep inertia, and have some brain fog as a result. They have gone on to investigate treatments that counteract GABA like the antibiotic clarithromycin and a compounded form of the IV drug flumazenil. However, this theory and its treatments have not really taken off the past few years since the initial research. Other theories revolve around circadian rhythm disorders, like delayed sleep-wake phase syndrome in which the body’s internal clock is set much later than one’s social clock, creating a mismatch between the person’s schedule and the body’s schedule, leading to symptoms similar to IH. I have seen cases in which the patient is in bed 10 hours per night but on their overnight sleep study, their brain is only getting 6-7 hours of actual sleep because the brain keeps going in and out of sleep frequently (sleep fragmentation). Their sleep quality is thus poor and they are very sleepy during the day, but this is not like classic IH. The cause of the fragmented sleep can be due to high levels of stress and anxiety for example, but the cause of fragmentation is often idiopathic. (These are typically difficult cases to manage but may improve with consolidation of sleep to improve sleep efficiency, i.e. constricting how much time they are in bed.) 

Only further research in upcoming years will give us answers. It is very likely that IH could be a mix of very rare conditions in which the resulting symptoms all look similar. This is why it is so helpful to know some underlying biology to explain what we are seeing, as in narcolepsy type 1. If we don’t have biology, then there had better be very classic symptoms to distinguish the condition from other mimics. Unfortunately, most who carry the diagnosis of idiopathic hypersomnia do not have it, if it is what it is. The upshot is that with age and life experience, other aspects of sleep can coincidentally improve over time, reducing the degree of symptoms, even in the case of continuing to be in the dark of the true cause of daytime sleepiness. The lesson here, as with narcolepsy type 2 and periodic limb movement disorder, is that common things are common. Idiopathic things are uncertain. Address the basic aspects of sleep and health first before looking for something that is rare, untreatable, and questionably diagnosed.

- Andy Berkowski, MD of ReLACS Health, who has adopted modern technology like telemedicine and word processors and did not write this with quill, ink, and paper