Hypersomnia Foundation

Posts Tagged 'cataplexy'

Ask the Doctor: Narcolepsy vs Idiopathic Hypersomnia

Ask the Doctor: Narcolepsy vs Idiopathic Hypersomnia:

What’s the Difference?

My 9-year-old son recently was diagnosed with IH but can’t exclude narcolepsy. We got a second opinion and the doctor agreed. I don’t understand why they don’t have a definitive answer. The doctors told me to not to worry about narcolepsy vs. hypersomnia. Can anyone help me understand the difference? And is it possible to have IH and beginning stages of narcolepsy?
Dr David Plante presenting at the Beyond Sleepy in the Mile High City Conference
Both narcolepsy and idiopathic hypersomnia (IH) are considered central disorders of hypersomnolence (CDH). They share similarities, most important of which is the requirement that patients with both disorders must experience significant excessive daytime sleepiness. From a diagnostic standpoint, sleep medicine uses the multiple sleep latency test (MSLT), a repeated nap study performed after polysomnography (PSG; an overnight sleep test), to help identify and characterize central disorders of hypersomnolence. One of the primary results of these tests used to determine whether a patient has narcolepsy or IH is based on the number of sleep onset REM periods (SOREMPs), during which individuals go into REM sleep much faster than is typical. Patients with narcolepsy have 2 or more SOREMPs on PSG/MSLT testing, where patients with IH do not.

There are differences in other clinical symptoms experienced by patients that can be used to help clarify whether a person has narcolepsy or IH. For example, patients with IH often sleep excessive amounts of time and have severe difficulty waking up after sleeping (i.e. excessive sleep inertia). Patients with narcolepsy frequently do not sleep excessive amounts of time, and may find brief naps refreshing. Many patients with narcolepsy also experience symptoms related to REM sleep instability such as sleep paralysis (waking from sleep in a paralyzed state) and hallucinations around sleep onset/offset, thought to be due to inappropriate combinations of REM sleep and waking brain function. In addition, some patients with narcolepsy experience cataplexy, the sudden loss of muscle tone in response to emotions such as laughter. Cataplexy is almost never seen outside of narcolepsy, and thus when patients have this symptom, there is high suspicion that the patient does indeed have narcolepsy.

Sometimes, the clinical history and results of PSG/MSLT testing do not neatly align. Although I do not have the specifics in the case of your son to comment definitively, it is certainly possible that the results of his sleep testing have shown he is pathologically sleepy consistent with IH, but did not have enough SOREMPs to be diagnosed with narcolepsy. He may also have clinical symptoms that are more suggestive of a narcolepsy diagnosis than IH, which is why there is some ambiguity around the diagnosis. Sometimes retesting can help clarify the diagnosis, but not always. Because initial treatment of both narcolepsy and IH often involves stimulants, oftentimes treatment is initiated for practical reasons to try to improve the patient’s symptoms, since the precise diagnosis may not alter initial clinical management, particularly in the early stages of treatment.

David T. Plante, M.D.
Assistant Professor, Department of Psychiatry
Program Director, Sleep Medicine Fellowship
University of Wisconsin School of Medicine and Public Health


Glossary of terms:

Central Disorders of hypersomnolence (CNS): As defined by the ICSD-3 rd –Include Narcolepsy Type 1, Narcolepsy Type 2, Idiopathic Hypersomnia, and Kleine- Levin Syndrome. They also include hypersomnolence caused by a medical disorder, medication or substance, psychiatric disorder and insufficient sleep disorder.

Rapid Eye Movement (REM) sleep: One of the two basic states of sleep. REM sleep, also known as dream sleep, is characterized by rapid eye movements, and more irregular breathing and heart rate compared to NREM sleep, the other basic state of sleep.

Sleep Onset REM Period (SOREMP): REM periods within 15 minutes of sleep onset, considered to support the diagnosis of narcolepsy.

Sleep Inertia: Feelings of grogginess and sleepiness that occur upon awakening that can result in impaired alertness and may interfere with the ability to perform mental or physical tasks.

Sleep Paralysis: involves the temporary inability to move, speak, or take a deep breath while falling asleep or waking up.

Hypnagogic or hypnopompic hallucinations: Sensory experiences involving the apparent perception of something that is not present, that occur at the transition from wakefulness to sleep (hypnagogic) or from sleep to wakefulness (hypnopompic). These hallucinations are typically visual in nature, but can affect other forms of sensation such as hearing or sense of touch.


 

Disclaimer for Ask The Doctor: The medical information provided is meant for educational purposes only and not as a substitute for professional medical care or advise.  Questions about a personal health condition should be discussed with your healthcare professional.

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What’s New in the Diagnosis and Treatment of Hypersomnia in 2016?

Rather than writing our own article for this week’s edition of SomnusNooze, we are bringing you information from Dr. David Cunnington in Melbourne, Australia. Dr. Cunnington has agreed to share with us a recent post from his website (sleephub.com.au) that covers hypersomnia-related topics from the SLEEP2016 meeting in Denver. A podcast, which covers hypersomnia and other SLEEP2016-related topics, is available at sleephub.com.au/podcast (click on Sleep 2016 Update).

From Dr. Cunnington
In clinical practice it can be difficult accurately diagnosing people with hypersomnia and excessive sleepiness. Apart from narcolepsy with cataplexy, or type 1 narcolepsy, where there are distinct symptoms, and the possibility of testing orexin levels in cerebrospinal fluid, it can be hard to make an accurate diagnosis. Managing people with hypersomnia can also be difficult, as a substantial proportion of people are refractory to treatment with currently available wake-promoting medication.
Issues around diagnosing and treating hypersomnia were discussed at the recent Sleep2016 meeting in Denver, and I’ve tried to summarise some of the main issues that were covered.

Issues With Diagnosing Hypersomnia
The International Classification of Sleep Disorders 3rd Edition (ICSD-3), divides central disorders of hypersomnolence into narcolepsy type 1 (with cataplexy), narcolepsy type 2 (without cataplexy), idiopathic hypersomnia (IH) and then a range of other hypersomnias secondary to medical or psychiatric conditions or medications and the rare condition, Kleine-Levin syndrome.
The criteria for the diagnosis of IH listed in ICSD-3 are:

  • The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least three months.
  • Cataplexy is absent.
  • A Multiple Sleep Latency Test (MSLT) performed according to standard techniques shows fewer than two sleep-onset REM periods or no sleep-onset REM periods if the REM latency on the preceding polysomnogram was less than or equal to 15 minutes.
  • The presence of at least one of the following:
    • The MSLT shows a mean sleep latency (MSL) of ≤ 8 minutes.
    • Total 24-hour sleep time is ≥ 660 minutes (typically 12–14 hours) on 24-hour polysomnographic monitoring (performed after correction of chronic sleep deprivation) or by wrist actigraphy in association with a sleep log (averaged over at least seven days with unrestricted sleep).
  • Insufficient sleep syndrome is ruled out (if deemed necessary, by lack of improvement of sleepiness after an adequate trial of increased nocturnal time in bed (preferably confirmed by at least a week of wrist actigraphy).
  • The hypersomnolence and/or MSLT findings are not better explained by another sleep disorder, other medical or psychiatric disorder, or use of drugs or medications

Whilst people with narcolepsy type 1 can usually be differentiated from these criteria, narcolepsy type 2 and hypersomnia associated with medical or psychiatric disorders can often overlap significantly with these symptoms. In addition, I often see people with most, but not all, of these symptoms. What do they have? They clearly have a problem, as they have been severely impacted by their symptoms and sleepiness. How much sleep and sleepiness is normal? Some surveys suggest around 8% of people sleep for more than 9 hours per day, and 1.6% of people report sleepiness intruding on their waking activities. One of the tests we commonly use, the MSLT, whilst helpful, can be negative in people with all the other symptoms of IH. In one study, 71% of people with long sleep times and other symptoms of IH had a mean sleep latency of > 8 minutes. In addition, unpublished data from Emory University has shown that around 50% of people with chronic fatigue syndrome meet the MSLT criteria for IH. Other studies have shown that 25% of people with hypersomnia due to psychiatric conditions have an MSL of < 8 minutes.

There really wasn’t any clear consensus on how exactly to define hypersomnias and IH. Unfortunately there are not good biological markers, and trying to make a definite diagnosis based on symptoms is fraught with difficulty. So an approach put forward by the team from Emory and that seems to make sense is to try to exclude other factors that can add to sleepiness symptoms, such as depression and circadian rhythm disorders, as well as getting a number of objective measurements of sleepiness and it’s impact. They do this by performing the below tests and assessments:

Although the team at Emory were testing cerebrospinal fluid levels of GABA potentiation in everyone with hypersomnia at one point, they are not doing this routinely at the moment and have found that people with sleepiness due to other causes such as sleep apnea can also have GABA potentiation, meaning that what they had previously described as a “somnogen” may not be specific for IH, but may in fact be a mediator of sleepiness symptoms in a range of conditions.

Options For People Refractory To Available Treatments

With regard to treatment, we often find people with IH are refectory to treatment, and some groups report around 50% of people on modafinil not persisting with treatment because of a lack of efficacy, and only 30% to 60% of people on dexamphetamine continuing with treatment. Given this, other treatments to address symptoms of sleepiness symptoms are needed.

Clarithromycin – has been used by the team at Emory who published their research in Annals of Neurology in 2015. In that study, they treated 23 people with clarithromycin, and they reported the results on 20 cases using clarithromycin 500 mg twice daily. They did not show changes in reaction time but did show subjective measures of sleepiness were significantly improved. People did get gastrointestinal side effects and changes in taste, so it was not well blinded, so it is a little hard to know exactly how to interpret that, but, nonetheless, this may be a helpful agent.

Flumazenil – has also been used at Emory. At the meeting, they presented their experience with 153 patients they treated between 2013 and early 2015. They administered flumazenil as sublingual lozenges or transcutaneous lotion. Overall, 63% of people felt flumazenil had helped their sleepiness, dropping the mean Epworth Sleepiness Score in the group from 15 to 10.3, and 39% of people remained on treatment at the end of the observation period, which was an average of 7.8 months. Interestingly, one of the predictors of clinical response was the presence of significant sleep inertia, with 72% of those with sleep inertia getting a good response versus 42% of those without sleep inertia.

Sodium oxybate (Xyrem) – is another treatment that was discussed for sleep inertia, which can be one of the most difficult symptoms to manage in people I see with hypersomnias. Whilst Xyrem is most commonly used in treating narcolepsy, Isabelle Arnulf from Paris has treated a number of people with IH with sodium oxybate. Their results, published in Sleep Medicine in 2016, showed that it can reduce morning sleep inertia and probably had a greater effect on this than on overall sleepiness symptoms.

JZP-110 – is a compound being developed by Jazz Pharmaceuticals that has both dopaminergic and noradrenergic activity. In two small clinical trials with a total of 126 subjects, it has been shown to increase the MSL on a Maintenance of Wakefulness Test by 8.9 minutes. This may not sound like much, but, in comparison, in the sentinel modafinil studies, MSL increased by 2.3 minutes, and, for dexamphetamine, there is a 5.6-minute change. So, at this stage, results for JZP-110 look promising, and it appears to be significantly more effective than modafinil or dexamphetamine. Larger phase 3 trials, aiming to enroll more than 800 subjects with sleepiness started in mid 2015, and results are expected at the end of 2016.

Non-drug treatments – There is increasing acknowledgement that medications only partially address symptoms of sleepiness and that there is a role for psychological and behavioural treatments to reduce the impact of symptoms in people with hypersomnias and other conditions that cause sleepiness. For people with narcolepsy with cataplexy, napping has long been used as a strategy, but for people with IH, napping as a strategy often doesn’t work, as they can’t have short naps and have significant sleep inertia on waking from naps. Research on behavioural strategies to help manage symptoms of sleepiness is now being undertaken, and I had a chance to talk with Assistant Professor Jason Ong about it at the meeting in the following interview: Sleep Talk: Episode 8 – Sleep 2016 Update.

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