A Life Consumed
By Sleep

Increasing awareness of a rare sleep disorder

An illustration of a young man lying in bed sleeping with a cityscape and a crescent moon showing through his window.

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Emory neurologist David Rye is an expert on sleep disorders such as restless leg syndrome, narcolepsy, and hypersomnia.

Nothing he tried had worked.

For Sigurjon Jakobsson, the trip to Atlanta with his family was a last-ditch effort to wake up. He had struggled with sleeping excessively for several years before coming from Iceland to see a visionary neurologist, who might have answers.

In high school, Sigurjon was a decathlete competing as part of Iceland’s national sports team. But at the age of 16, an increasing need for sleep began to encroach upon his life. Sigurjon needed several alarm clocks to get out of bed and was frequently late to school or his job at a construction company. He often slept more than 16 hours in a day.

When Sigurjon describes his experiences, they sound like depression, although his mood and lack of motivation appear more a consequence of his insatiable desire to sleep. He quit sports. He dropped out of college and became isolated and lost touch with close friends.

“Your will to do things just kinda dies,” he says. “And then you’re always trying and trying again. It just gets worse. You kinda die inside from being tired all the time.”

At the recommendation of a neurologist in Iceland, Sigurjon’s family sought out Emory Brain Health Center’s David Rye, who is known internationally for his research on idiopathic hypersomnia, a poorly understood sleep disorder.

A photo of patient Sigurjon Jakobsson with electrodes on his head.

Sigurjon Jakobsson came to Emory from Iceland for diagnosis and treatment of his sleep disorder.

Sigurjon Jakobsson came to Emory from Iceland for diagnosis and treatment of his sleep disorder.

Sigurjon’s profile suggested that he might respond to an unconventional medication Rye has experience with: flumazenil. It was not originally developed for use with sleep disorders and is generally given intravenously. It is available in an oral lozenge form and in a cream applied to the skin only through a few compounding pharmacies in the United States. That’s why Sigurjon had to come to Atlanta to try it.

After evaluating his medical history and symptoms, and giving him a series of tests, Rye concluded that Sigurjon has idiopathic hypersomnia.

 “When you listen to him,” Rye says, “he sleeps too much, he has a hard time waking up, he takes long naps, he has ‘sleep drunkenness’…that’s hypersomnia.”

Redrawing the map

Over the last several years, Rye has been calling attention to the neglected status of idiopathic hypersomnia, or IH. Hypersomnia means “too much sleep,” but the word idiopathic can be confounding. It means the cause is not known.

Sleep scientists have argued about IH’s origin and mechanisms, and whether it’s one, two or many entities. Rye and his team have an idea for how to redraw the map.

"We're trying to change sleep medicine here," Rye says. "We want to at least get patients in through the right doorway so that we can direct them more swiftly to an accurate diagnosis and a tailored treatment.”

Sleep specialists are trained to recognize conditions that can render someone drowsy, with two of the most common being sleep apnea and narcolepsy. Sleep apnea comes from interruptions in breathing, which interfere with sleep’s restorative nature and put strain on the heart. Narcolepsy—one form of it, at least—is also well-understood: an autoimmune attack eliminates cells in the brain that keep someone awake and alert.

But some people with persistent sleepiness don’t fit neatly into these categories. Understanding what lies behind their sleepiness could unlock new insights into how the brain works. It could also change the lives of people, such as Sigurjon, who have slipped through the cracks of modern medicine.

A t-shirt design of an apple and an orange, with the words: Hypersomnia, consumed by sleep. Narcolepsy, seized by sleep.

Sleep researcher David Rye's T-shirt design contrasts narcolepsy (seized by sleep) and hypersomnia (consumed by sleep), saying that comparing the disorders is like comparing apples and oranges.

Sleep researcher David Rye's T-shirt design contrasts narcolepsy (seized by sleep) and hypersomnia (consumed by sleep), saying that comparing the disorders is like comparing apples and oranges.

Rye compares hypersomnia and narcolepsy to apples and oranges. (He even created a T shirt design to drive home this point.) He has proposed that in some people with symptoms like Sigurjon’s, the circuits within the brain that promote and maintain sleep are overactive. This idea is supported by the Emory team’s use of flumazenil for IH and similar disorders.

Flumazenil is an antidote against benzodiazepines and related compounds, a class of anti-anxiety and sedative drugs, such as alprazolam (Xanax), zolpidem (Ambien), diazepam (Valium), and midazolam (Versed). People undergoing an uncomfortable medical procedure, such as a colonoscopy, are often given Versed for “conscious sedation.” If they get too much and have trouble breathing, flumazenil can reverse the sedation. It can also be used to counteract overdoses of other benzodiazepines in the ER.

In 2007, Rye and his colleagues observed flumazenil’s effects with Anna Sumner Pieschel, an Atlanta attorney whose life was being overtaken by sleep. Anna had to take a leave from her job and couldn’t drive. She already had tried conventional medications, such as the “smart drug” modafinil, together with amphetamines. Anna found it difficult to tolerate the doses she needed to stay awake and experienced periodic crashes.

Rye has compared Anna’s treatment with stimulants to “driving a car with the parking brake on.” He and a colleague, nurse practitioner and sleep researcher Kathy Parker, suspected something else was going on. Laboratory tests indicated that her spinal fluid mimicked the effects of benzodiazepines, even though she wasn’t taking any. A more extensive account is in this 2013 Emory Medicine article.

A photo of Emory sleep researchers David Rye and Andrew Jenkins with hypersomnia patient Anna Sumner Pieschel.

Emory neurologist and sleep researcher David Rye (left), Andrew Jenkins (center), and patient Anna Sumner (now Pieschel), while Anna was being treated for idiopathic hypersomnia (IH) at Emory. Jenkins is investigating the biochemistry behind IH and flumazenil.

Emory neurologist and sleep researcher David Rye (left), Andrew Jenkins (center), and patient Anna Sumner (now Pieschel), while Anna was being treated for idiopathic hypersomnia (IH) at Emory. Jenkins is investigating the biochemistry behind IH and flumazenil.

Looking for alternatives for Anna, Rye and Parker obtained some flumazenil from manufacturer Hoffmann-La Roche, through a limited “compassionate use” arrangement. They figured out how to deliver it as under-the-tongue lozenges and a skin cream. Flumazenil—in combination with other medications—helped Anna return to work. She eventually became a partner at her firm and felt confident enough to get married and start a family.

Nodding toward her energetic preschool-aged son, Anna says: “If you told me six years ago that this would be my life, I wouldn’t have thought it was possible… Today I have everything I never thought I would have.”

Anticipation of a different life

Sigurjon’s family, and some of the doctors he saw in Iceland, were unsure how to help him. He had already tried other medications that are often used to treat persistent sleepiness: modafinil and methylphenidate (Ritalin). They could physically keep him awake, but he still didn’t feel right.

In July 2018, Sigurjon, then 23, got a chance to let a flumazenil lozenge dissolve under his tongue. As seen in the Georgia Public Broadcasting video, both his family and Anna were watching. The effect was not immediate. In July 2018, Sigurjon, then 23, got a chance to let a flumazenil lozenge dissolve under his tongue. As seen in the Georgia Public Broadcasting video, both his family and Anna were watching. The effect was not immediate.

“They did nothing but keep me from falling asleep when I was tired,” he says. “This is my last resort. If this doesn’t work, I don’t know.”

by Quinn Eastman

Emory neurologist and sleep researcher David Rye in a white coat in a lab.

Emory neurologist David Rye is an expert on sleep disorders such as restless leg syndrome, narcolepsy, and hypersomnia.

Emory neurologist David Rye is an expert on sleep disorders such as restless leg syndrome, narcolepsy, and hypersomnia.

Quickly: Take a nap

Sigurjon was actually diagnosed in 2016 in Iceland with a form of narcolepsy: type 2, or narcolepsy without cataplexy. Cataplexy is a distinctive symptom, which is tightly associated with the type 1 autoimmune form of narcolepsy: muscle weakness triggered by emotions or stress.

People with narcolepsy who do not have cataplexy are usually diagnosed through the Multiple Sleep Latency Test. In this test, someone is asked to take four or five naps throughout the day. If they zonk out quickly enough, averaging a delay of less than 8 minutes, and enter REM sleep during two or more naps, then a narcolepsy diagnosis applies. If they fall asleep quickly, but don’t enter REM sleep, then idiopathic hypersomnia (IH) applies.

The IH diagnosis more properly applies to Sigurjon, Rye argues.

A photo of neurologist Lynn Marie Trotti sitting down with a brain imaging cap on, and research associate Prabhjyot Saint preparing for a test run.

Neurologist Lynn Marie Trotti (seated) with research associate Prabhjyot Saini, preparing for a test run on her brain imaging study. (Photo courtesy of Diana Kimmel.)

Neurologist Lynn Marie Trotti (seated) with research associate Prabhjyot Saini, preparing for a test run on her brain imaging study. (Photo courtesy of Diana Kimmel.)

David Rye and Lynn Marie Trotti have shown that the sleep latency test works well for type 1 narcolepsy but provides inconsistent results for people with type 2 narcolepsy and IH. That is, the test can put someone in one of those last two categories, but if they take the test again, they will often get a different result. This happened to Sigurjon.

Overall, the finding supports Rye and Trotti’s call that the map of sleep disorders needs to be redrawn. Other sleep scientists have agreed that additional diagnostic criteria for IH, such as monitoring how many hours someone sleeps throughout the week, are valid. More discussion on how to revise the categories is underway. Under current criteria, the prevalence of IH is estimated to be around 1 in 3,000.

A graphic depiction of a bed in a dark room.

Want to know more?

Please visit Emory's Frontiers of the Brain website, the Emory News Center, and Emory University.