Differential Diagnosis of Idiopathic Hypersomnia

Sree Roy:

Hello and welcome. I’m Sree Roy with Sleep Review and I’m thrilled to be here with neurologist-sleep specialist Yves Dauvilliers, MD, PhD, professor of Neurology and Physiology at the University of Montpellier, France. His research focuses on the diagnosis, epidemiology, pathophysiology, and therapy of sleep disorders, particularly neurological disorders such as idiopathic hypersomnia, narcolepsy, and restless leg syndrome.

This episode is sponsored by Jazz Pharmaceuticals.

Today we are chatting about differential diagnosis of idiopathic hypersomnia.

Idiopathic hypersomnia can be particularly challenging to diagnose because of its lack of specific biomarkers as well as its symptoms resembling those of other disorders. How do you differentiate idiopathic hypersomnia from hypersomnia of a specific cause, such as narcolepsy type 1 and type 2, insufficient sleep syndrome, or hypersomnia due to a neurodegenerative disease?

Dr. Yves Dauvilliers:

Yes, this is the very important point. The first step is to make a good clinical interview; for specific example, namely cataplexy because that exists only in narcolepsy type 1. You need to also to look for hypnagogic hallucinations, sleep paralysis that exists in narcolepsy type 1 and type 2. If you want to focus a lot on IH it’s mostly the long sleep duration, so-called hypersomnia, and excessive daytime sleepiness that is shared by narcolepsy type 1 and type 2 as well. But they are often not refreshed in the morning and after naps in the context of IH. So this is the first step, and also you need to exclude for sure sleep-deprived (so chronic sleep-deprived) and also comorbid condition, psychiatric condition, neurological condition with headache, migraine, Parkinson’s disease, traumatic brain injury. So every disorder that may mimic or be associated with the complaint of excessive daytime sleepiness. So this is the clinical interview.

And the second step is to perform MSLT to look for this sleepiness and the dysregulation of REM sleep. This is the pattern of narcolepsy, type 1, type 2. For IH the long sleep duration during the night and sometimes even during the day. In this second step you will exclude sleep-disordered breathing, you will exclude a lot of disorders that may mimic this hypersomnolence.

The third step, sometimes you need to go a little bit further with orexin measurement within the CSF, with the lumbar puncture, you can also prescribe HLA if it’s HLA-DQB1*06:02 for the narcolepsy and for the neurogenetic disorder you can perform also some MRI or CT scan, either some neurological condition such as headache or some abnormal in your neurological exam.

So there are three steps. First clinical interview. Second is sleep lab assessment and third is depending on the context, cases by cases, if you need to do for biological or neuroimaging biomarker.

Sree Roy:

A minority of people simply need to sleep longer than most, even 10 hours or more to feel refreshed. How do you determine if that applies to a given person who may not have a sleep disorder at all?

Dr. Yves Dauvilliers:

Yes, you really need to differentiate what is a long sleeper and what is IH. Because a long sleeper that exists is extreme normal variant, I may say. So the patient can, not the patient but the subject, can sleep 9, 10, 11 hours. Mostly they are young, they and they are no complaint during the day that they sleep more than expected. But at the end they feel refreshed in the morning and they can have a normal daily life. There’s no sleepiness during the day.

In contrast, IH subject will sleep as long as this long sleeper, more than 9 hours, sometime 10, 12 even more. But they have also sleep inertia in the morning and they have long naps during the day with excessive daytime sleepiness. So that’s really different story. The patient with long sleep only, so it’s not the patient is the subject, will never go to see you except, and this is a little bit more complex: if they are sleep-deprived—because most of daily life you cannot sleep 10 hours or 11 hours. So if you need that but you cannot because you need to wake up to work, you will be sleep-deprived. Because when we say sleep-deprived mostly seven hours, if you have seven hours of sleep, you are not sleep-deprived. But if you need 10 and you can sleep just eight, you will be sleep-deprived by two hours. So the story is always complex.

What is sleep-deprived? It depends on your biological need and that may change and evolve with decades. If you are 20 years old or 40 years old, your need may differ as well.

Sree Roy:

How do you differentiate idiopathic hypersomnia from hypersomnia comorbid to psychiatric disorders, such as prolonged sleep time tied to depression?

Dr. Yves Dauvilliers:

Yes, again, for this important question, you need again a two-step assessment.

The first is a good clinical interview. You need to look for depression, could be major depressive disorder, could be bipolar disorder. To do so, you need also, in addition to your clinical interview, the help of some questionnaires such as the Beck Depression Inventory as an example, to quantify these depressive symptoms.

If the depression is, as a first step, as the major symptoms, often you need to manage depression as a first step.

Sometimes it is comorbid to hypersomnia and you need to go to the second step to record sleep in the lab during the night, during the day, and to be sure that there is no hypersomnia that may be again comorbid with depression. One example, the patient is with IH for decades or at least several years without any diagnosis, without any correct management it can be depressed.

So because of this disorder, which is not diagnosed and not managed correctly. So it’s not because the depression exists that there is no IH. But often it’s not exactly the same big symptoms as a primary complaint. If you recall the sleep and you have long sleep duration during the night and long naps and not refreshed after adding two hours or three hours of nap, it will be IH.

So we do have some biomarker in term of neurophysiological assessment of IH and for depression. If you put patient with depression in the lab, he will have very bad sleep at night and in-between sleepiness during the day. There’s some complaint but it’s not objectively assessed.

Sree Roy:

We’ll be right back with Dr Dauvilliers after the short break.

This episode is sponsored by Jazz Pharmaceuticals. Jazz Pharmaceuticals is a global biopharmaceutical company with a focus in neuroscience and sleep medicine committed to improving the lives of patients and their families. Jazz is also the proud creator of sleepcountshcp.com. The goal of sleepcountshcp.com is to increase awareness of idiopathic hypersomnia and support symptom recognition to help patients receive a quality diagnosis and appropriate disease management. Sleepcountshcp.com provides evidence-based educational materials and resources to improve communication between healthcare professionals and their patients. Visit jazzpharma.com and sleepcountshcp.com for more information.

At what point in ruling out other disorders should objective sleep testing, such as polysomnography and multiple sleep latency testing, be done?

Dr. Yves Dauvilliers:

Yes, that the excellent point. When you have in mind that sleepiness is really the primary complaint of the subject, long sleep at night and sleepiness during the day, you need all the time to confirm this hypersomnia. So the long sleep duration, so-called hypersomnia, and the daytime sleepiness. You need to do that for all subjects. If your test is abnormal, you will confirm the hypersomnia and/or the excessive daytime sleepiness.

The second step is why. If the patient is affected with a comorbid disorder such as depression, you can explain to the subject that they may be affected with both conditions.

If there is just this hypersomnia and/or excessive daytime sleepiness, but no neurogenetic disorder, no psychiatric disorder, no substance intake, it will be called idiopathic. So IH, idiopathic hypersomnia.

So it’s two steps. First is to confirm the diagnosis of hypersomnolence, so hypersomnia and or excessive time sleepiness. Second, is to be sure of the term idiopathic to exclude all the disorders that may better explain this hypersomnolence.

Sree Roy:

Why is idiopathic hypersomnia sometimes confused with sleep-breathing disorders? When would you recommend a CPAP trial to address possible apneas, hypopneas, or respiratory event-related arousals?

Dr. Yves Dauvilliers:

Yes, good point as well. We already touched that a bit with the second part of idiopathic, you know? You can have a long sleep duration and especially excessive daytime sleepiness associated with mild/ moderate AHI. Mostly it’s not severe, the AHI, but in mild/moderate cases with sleep-disordered breathing, it could be associated with excessive daytime sleepiness for sure because it’s a part of the sleep-disordered breathing symptoms. So how to be sure that hypersomnolence is due to AHI or due to an idiopathic condition?

There is two step as well. The first is a good clinical interview. We are doctors; we need to focus on good clinical interview. Mostly IH are young female, they are lean, they are not obese, and they start the disease around 15, 20 years old. But if they are not diagnosed because it’s an orphan disease, after 20 years of evolution, you can’t hear the patient after around 40 years old with a 20 years of history of this disorder, and at that time they can be a little bit overweight or even obese.

But when did this disorder start, when excessively daytime sleepiness start? So you need to focus on this long history of the clinical symptoms, and in cases of doubt because sometimes it is not like for depression we discussed; sometimes you have in mind it could be both problems, so abnormal HI, so OSA subject and hypersomnolence. If you have some doubt, you propose the treatment of OSA with a CPAP machine, and you reassess the hypersomnia and the excessive daytime sleepiness. Just to confirm if this problem persists and if that persists, it could be IH as well.

Sree Roy:

How do you distinguish chronic fatigue syndrome from idiopathic hypersomnia?

Dr. Yves Dauvilliers:

The first point I want to raise is, again, we need to objectify the excessive daytime sleepiness and the hypersomnia. Excessive daytime sleepiness is often done in many sleep lab because of the MSLT, but the long sleep duration at night, you need to do that 24 hours continuous recording to quantify the total sleep time. This is rarely done in US labs because of the cost and the insurance company that will not cover that in routine. I insist on that because if there is hypersomnolence disorder, so hypersomnia, and/or excessive daytime sleepiness, it’s not fatigue. It’s hypersomnolence.

The story is a little bit more complex because fatigue may coexist with hypersomnolence, but it is not alone. If there is no hypersomnia, no excessive daytime sleepiness, it cannot be IH. It is fatigue. But you can have fatigue associated with hypersomnia. So to separate, to quantify, to differentiate chronic fatigue syndrome and IH is, again, the second step to confirm existence of abnormal, excessive daytime sleepiness and/or abnormal hypersomnia.

So the first step is to listen to the patient, to look for the sleep inertia, the brain fog, the fatigue, the daytime sleepiness. The second is to confirm with objective assessment, and in the case of chronic fatigue, they are nothing abnormal related to sleep.

Sree Roy:

Thank you so much for chatting with us about differential diagnosis. You can find Sleep Review at sleepreviewmag.com. Thank you so much for tuning in to this episode.