LESSONS FOR IH

  As investigations of short sleep families suggest, it is unlikely for long sleep IH to be caused by only one type of mutation, such as a mutation in a circadian clock component. When German or Japanese research teams used the candidate gene approach to look for circadian clock mutations in IH, they did find a few associated variants.64 However, the associations were weak, similar to those reported in the GWAS study of essential hypersomnia, and individuals with long sleep duration were not separated out. Genetic studies of patients diagnosed with IH also have the potential to detect inherited conditions with overlapping symptoms, such as myotonic dystrophy.

  Other genes related to IH may include those responsible for sensitivity to sleep deprivation or sedatives.65 As stories in this book show, idiopathic hypersomnia has emerged as a clinical topic of interest partly because caffeine and conventional stimulants were unsatisfactory options. Thus, a reduced response to caffeine or stimulants or an inability to tolerate them may be a factor appearing in genetic analysis of IH because of altered drug metabolism or heightened aversive effects. For a large number of people with IH, their increased need for sleep was not present at birth but emerged around adolescence, with triggering events such as a viral infection or anesthesia. Thus, the underlying biology may be sensitivity of neural sleep-wake circuits to injury, possibly bearing some similarity to narcolepsy type 1.

  CHAPTER 12

  IMMOBILIZED BY HAPPINESS

  One of my objects here is to rescue the word narcolepsy from the confusion that now surrounds it, and to reinstate it as the name of a highly remarkable and by no means very rare disease, with peculiar and unmistakable features that distinguish it from epilepsy and all other morbid conditions in which excessive or untimely sleep is an occasional symptom.

  —William Adie, 1926

  This book focuses on idiopathic hypersomnia, but we’ve spent a lot of time comparing IH to narcolepsy. Narcolepsy has a longer history, more scientific information is available about it, and sleep medicine specialists have been trained to recognize it. Current understanding of the type 1 form of narcolepsy represents a scientific success story—one that carries both clues and distractions for those interested in IH.

  A central part of narcolepsy type 1 is the symptom of cataplexy. Let’s hear from someone who lives with it: Ann, whom I met through a narcolepsy support group organized by her mother. Ann distinctly remembers the first time she experienced cataplexy. She was in her junior year of high school. She was at her church in north Atlanta, and it was Youth Sunday, when she and her peers would be playing lead roles in the service. Ann was feeling excited and happy. She had to fetch something in an area of the church where not many people were. “Suddenly, my legs just didn’t work anymore,” she recalled. “And my body didn’t want to sit up. It was very uncomfortable.”

  At church, she could still call her mother with her cell phone. Another adult tried to help her onto a bench and then outside, to her mother’s car. The odd paralysis of her legs went away after a few minutes. Over the next few weeks, it started happening more often. Sometimes her legs would kick involuntarily, and her shoes would go flying. “For me, cataplexy always occurs legs first,” she said. “Like someone poking me in the back of the knee.”

  One day at school, she was late for science class, and the teacher shut the door and locked her out. She was looking in the window, saying “Let me in, please.” Her legs buckled. Unfortunately, she was standing on a concrete floor, and she hit her head on the concrete and experienced a concussion. As a result, teachers and administrators became concerned about her cataplexy events. They didn’t know exactly what was happening, but they didn’t want any more concussions or potential legal liability. Seeking a temporary remedy, her father—a mechanic—took a racing car harness and attached it to a wheelchair. During class, she was supposed to stay in the restraints. “I hated that wheelchair,” she said. “Half of the time, I used it as a book cart and would push it from class to class.”

  For most of her junior year, Ann was experiencing cataplexy several times per day—although she didn’t know what to call it. The collapses tended to occur when she was excited. At church youth group gatherings, a refrain was: “Don’t make Ann happy.” She would make sure to sit down if someone had good news. She didn’t avoid church or her friends (“I did avoid concrete”), but she did tend to remove herself from social situations and become more passive, zoning out watching television. A girl she considered a friend began talking behind her back, saying that she was faking to attract attention from boys.

  At one point, Ann was swimming at a neighborhood pool. She saw a family friend’s toddler behaving in an amusing way—and she suddenly couldn’t move enough to stay above the water. Her mother had to jump in and enlist others to lift her out. “It was the scariest moment of my life,” she said. “To this day, I won’t go to that pool by myself. I didn’t want to go to the beach for a long time.”

  During this period, Ann thought of herself as “a sleepy teenager.” She took naps at school—sometimes a few times a day, other times once a week. A few times she slept almost the entire weekend: going to bed Saturday and getting up on Monday, waking up just long enough to change clothes and use the bathroom. However, in terms of disrupting her life, cataplexy was at the forefront.

  She and her mother visited many doctors trying to understand what was behind these events. Their interpretations were colored by her previous medical history. In high school, Ann was already seeing a therapist and taking an antianxiety drug (buspirone), following her parents’ divorce. Initially, doctors thought that her sudden collapses were anxiety related. One diagnosed her with conversion disorder—what was called hysteria in the nineteenth century—and prescribed hypnotherapy.

  The next proposed diagnosis was epilepsy. After a difficult premature birth and a febrile seizure she experienced as a small child, Ann had taken an antiseizure medication for a while. Perhaps the seizures had returned? The idea was reasonable. Epilepsy was much more common than narcolepsy.

  Ann visited the epilepsy monitoring unit at an Atlanta-area hospital and underwent a seventy-two-hour EEG examination, during which she waited for a putative seizure to occur. For support, her mother invited someone she liked and trusted—the youth director from her church—to come to the hospital. “He walked in the door, and down I went,” she said.

  Even then, doctors and others at the epilepsy unit didn’t recognize what had happened, and she left without a definite diagnosis. As another explanation for her falls, a pediatric cardiologist proposed dysautonomia, or difficulty regulating blood pressure, causing dizziness. After a collapse, her mother was supposed to place a bulky heart monitor on her chest and record its signals—but this revealed that her heart’s rhythms were normal.

  Around this time, her mother had been Googling extensively and had come across the term “drop attacks”—or sudden falls without a loss of consciousness. A neighbor who was a doctor had mentioned another term, cataplexy, but it hadn’t caught on with other doctors they saw. “We had this word,” she said. “We told the doctors, but they didn’t necessarily agree.”

  In the end, a neurologist Ann and her mother found confirmed what they had been suspecting, saying: “You fall down when you get excited—that’s cataplexy.” Ann had been taking a low dose of an antidepressant—an SSRI (selective serotonin reuptake inhibitor). At the neurologist’s suggestion, she doubled the dose. The frequency of her falls decreased from several per day to every other day or even once a week.

  Ann was formally diagnosed with narcolepsy with cataplexy in September, when she was starting her senior year of high school. She and her mother had already figured it out anyway. Her MSLT was inconclusive because construction noise prevented her from falling asleep quickly. But in retrospect, the puzzle pieces fit together: her sleepiness, along with what she came to recognize was cataplexy and its response to antidepressants.

  Assembling a complex regimen of medications helped Ann continue her education. She only considered schools close to home, opting for the Atlanta campus of Savannah College of Art and Design. There, employees at the office that organized accommodations for students with medical needs were helpful, having dealt with another student with narcolepsy the year before. At her SCAD graduation ceremony, a celebrity (Oprah Winfrey) came to give a surprise speech. “As I was walking away, my legs were shaking like crazy,” she recalled. But she didn’t fall.

  Ann credited the expensive but effective nighttime medication Xyrem with controlling her cataplexy and making the episodes rare. Despite the rigid daily routine imposed by Xyrem, she recommended it to others, saying: “It keeps me vertical.” In 2014, she went to Disney World—full of exciting rides—without experiencing any cataplexy events.

  Although Ann’s symptoms were relatively well controlled, dealing with narcolepsy had drained her confidence. She was living at home, even after finishing college and finding a job at a museum. When her mother would travel outside Atlanta, she’d ask a friend to come stay with her. Although she had obtained her drivers’ license just before her cataplexy appeared, she avoided driving. She still wore a bracelet that instructed others not to call an ambulance if they found her in a state of temporary paralysis, although that didn’t happen very often.

  While every person with narcolepsy and cataplexy is different, Ann’s situation does represent aspects of what many experience: a glass half full. Confusion at the beginning but support and recognition available from a well-established community after diagnosis. Since the 1980s, the national organization Narcolepsy Network has held annual meetings, where people with narcolepsy can meet others with similar concerns. In the United States, there are local in-person support groups, supplemented in recent years by online groups.

  Support is necessary because narcolepsy is a major detour on life’s road. In a 2013 survey of more than 1,400 people with narcolepsy in the United States, most said that the disorder limits their performance at work or school. It constrained their ability to express emotion, drive safely, and interact with family and friends. Medications can provide substantial improvement of daytime sleepiness and control of cataplexy, but most people with narcolepsy still experience residual sleepiness.1 A substantial fraction do not take any medications, possibly because of unpleasant side effects.2

  In the past, narcolepsy advocates used bleak terms to discuss how their conditions affected their lives. As recently as 1990, the secretary of the American Narcolepsy Association (the predecessor of Narcolepsy Network) submitted testimony to a Senate committee, saying: “Most victims of narcolepsy spend their lives moving from job to job after being fired because they are considered lazy. However, many narcolepsy victims are totally disabled and do not lead much of a life at all.”

  It would be disturbing to hear that kind of pessimistic “victim” language today. Part of the shift comes from real change. Compared with thirty years ago, more medications are available that help people with narcolepsy manage their symptoms, work full time, and generally participate in life. There has also been a brightening of tone; the narcolepsy community now celebrates those who are leading lives of connection and accomplishment, aiming to encourage people with narcolepsy and show them that they are not alone. Still, when it comes to awareness and diagnosis, there is room for improvement.

  CONFUSION AND DELAY

  It took more than a year between the onset of Ann’s symptoms and a correct diagnosis. This is typical. In the 2013 survey of people with narcolepsy, most reported a delay of three or more years between symptom onset and diagnosis, and this overall picture of delay has persisted.3 A minority of primary care physicians in the United States could name both excess daytime sleepiness and cataplexy as the most prominent symptoms of narcolepsy.4

  A smaller Swiss study had similar findings: more than five years between onset and diagnosis, usually because of insufficient knowledge of narcolepsy in the treating physician. On average, at least three doctors were seen before a correct diagnosis.5 Common misdiagnoses were sleep apnea, depression, blood pressure dysregulation, iron deficiency, and more subjective judgments: “burnout,” “psychosomatic,” and “puberty related.” A Yale study found a striking years-long delay in narcolepsy diagnosis among women compared with men.6

  In the U.S. survey of people with narcolepsy, two factors predicting a longer diagnostic delay were pediatric onset and the absence of cataplexy. Without recognition of cataplexy, doctors are more likely to interpret excess daytime sleepiness as a symptom of depression or sleep apnea, which are more common conditions. The other symptoms of narcolepsy can be misleading. Substantial weight gain at disease onset can lead doctors to investigate a possible metabolic or endocrine disorder. Hypnogogic hallucinations can be interpreted as a sign of schizophrenia.7

  Exceptions do occur, when a few patients accurately diagnose themselves and come into a doctor’s office with a description of cataplexy printed out. And in both North America and Europe, diagnostic delays do seem to be getting shorter, possibly reflecting increased awareness. Still, as a matter of necessity, these studies leave out people with narcolepsy or IH who have not been able to access a specialist or are assumed to have depression, sleep apnea, or another condition.

  INTIMATE DISRUPTOR

  One factor complicating and delaying narcolepsy diagnosis is that cataplexy is difficult to observe in a hospital or clinic setting because a certain intimacy or comfort level is necessary to evoke it. Even an experienced sleep specialist may have witnessed cataplexy in person only a handful of times. Doctors depend on asking patients or their families to describe what they’ve experienced or seen. Home videos can help.

  The precise emotional triggers that bring on cataplexy vary from person to person. For most, it’s not stress or social anxiety. While laughter is the strongest, telling a joke can be just as powerful as passive amusement. Julie Flygare, author of a memoir about narcolepsy, told me she could visit and enjoy a comedy club without trouble. Although she was effectively medicated like Ann, she still might experience cataplexy if she unexpectedly saw a friend or an animal near her house.

  Severe cataplexy can lead someone to suppress their emotions and push them away from social interactions with friends and loved ones. One example is the Oregon neuroscientist Matt Frerking, profiled in 2010 by This American Life. Speaking in a flat tone of voice, Frerking told an interviewer that he tried to enjoy things less and thought of himself as a robot. The radio program recounted stories about him falling into a flower bed and being unable to pet a puppy or attend a toddler’s birthday party without collapsing.8 His wife, Trish, wrote on her blog: “He’s missed weddings, birthdays, and pretty much all of our family gatherings. He has to completely avoid interacting with our grandkids, spending any time he is in the same house with them off by himself in a quiet room, either working on his laptop or napping.”9

  Frerking’s story inspired the 2019 film Ode to Joy, which framed cataplexy as an obstacle to romance. This movie was a more humane, empathetic vision of cataplexy than crude comedies such as Deuce Bigalow, but it still contained some inaccuracies. While some people with narcolepsy do take steps to try to push off cataplexy, such as tensing their muscles to avoid laughing, the techniques portrayed in the movie, such as listening to funeral music on the way to work or jabbing one’s foot with a tack, are not likely to work.10

  In some people with narcolepsy and especially in children, cataplexy can appear more subtly.11 It may affect only part of the body, such as the face or arms, or it can appear as disturbed gait or repetitive movements of the fingers or tongue, without an obvious emotional trigger. In a video shown at a narcolepsy conference, a group of children from the Netherlands were at a birthday party, clapping their hands and singing a song. One girl kept clapping, but her face was distorted and her mouth was agape, the only indicators that she was experiencing partial muscle weakness. Cataplexy often changes as a child becomes older, shifting to the form more typical for adults.

  The age-related differences can lead to problems when doctors impose assumptions about narcolepsy in adults onto children. In her memoir Waking Mathilda, Claire Wylds-Wright describes missed chances to diagnose her daughter, then three years old.12 Wylds-Wright tells how her daughter experienced disturbed nighttime sleep and vivid hallucinations. Doctors first thought Mathilda had a brain tumor because of her wobbling gait and then referred both mother and daughter to psychiatrists. Narcolepsy was erroneously ruled out because her daughter didn’t collapse after a quick surprising tickle.

  CONDUCTORS OF THE ORCHESTRA

  Both Ann and Anna Sumner were young women in the Atlanta area with neurological sleep disorders. Their first names may be similar, but there is a critical difference. Although Ann’s diagnostic journey had more twists and turns, scientists now know much more about what lies behind her condition: narcolepsy type 1, also known as narcolepsy with cataplexy. For Ann’s sleep disorder, a wealth of research has shown that the problem lies with part of the hypothalamus.

  In narcolepsy type 1, an overreaction by the immune system appears to rub out a group of neurons in the hypothalamus. This selective process leaves neighboring neurons intact. We will discuss in more detail how this happens in the next chapter; for now, let’s focus on what these neurons do. They produce a neuropeptide called hypocretin, which plays a critical role in stabilizing the “flip-flop” switches we discussed in the previous chapter. These are the connections between the sleep-promoting VLPO and other wake-promoting areas in and near the hypothalamus. It explains why people with narcolepsy type 1 have disturbed nighttime sleep as well as trouble staying awake—in the absence of hypocretin, sleep-wake transitions take place more readily.