In the Swiss study, significantly fewer people experienced strong levels of subjective daytime sleepiness: 12.5 percent of men and 5.9 percent of women. There was no statistical association between frequency of disruptions in breathing and Epworth Sleepiness Scale scores.46 A retrospective review of sleep clinic patients at the Mayo Clinic obtained a similar result: ESS scores do not correlate with the severity of breathing problems, especially for women.47 People evidently have a wide range of sensitivities to the nighttime arousals that breathing disturbances trigger.

  The bottom line is that many people experience excessive daytime sleepiness, but fewer go through a rigorous diagnostic process, exhaustively checking potential causes. Sleep apnea has the most obvious overlap with IH, but other possibilities include depression, hypothyroidism, even hepatic encephalopathy. As we see it today, IH is partly created by deficiencies in the health care system, but potential scientific value may lie in understanding those who fall through the cracks.

  CHAPTER 5

  BEHIND THE CURTAIN

  One might be tempted to view the pre-REM era of sleep and dream research as a dark age illuminated feebly by Freud and the reticular formation, while the post-REM days provide untarnished enlightenment. Not precisely so.

  —Eugene Aserinsky, “Drug and Dreams, a Synthesis,” 1969

  Where did the concept of idiopathic hypersomnia come from? The nineteenth-century medical literature includes descriptions of people who might have been diagnosed with IH today.1 Early sleep researchers such as Nathaniel Kleitman defined hypersomnia as “uncontrollable somnolence and pathologically prolonged sleep, from which it is sometimes difficult to arouse the sleeper, or to keep him awake for any length of time after he has been awakened.”2

  That said, the clinical profile of IH comes from Bedřich Roth (figure 5.1). He was the first sleep researcher to distinguish IH from other sleep disorders, conceiving it as the other end of a spectrum including narcolepsy. While studying patients with narcolepsy during his medical training and early career, Roth encountered other patients whose characteristics were different. They made him think that sleep drunkenness, or prolonged clumsiness and confusion after waking up, was both a symptom and a key feature of a separate illness, now called IH.

  Roth’s ideas began to take form before the transformative studies of the 1960s, when narcolepsy was tied to aberrations of REM sleep. They also predate the rise of clinical sleep medicine in the United States and Europe. His situation in Cold War–era Czechoslovakia, separated from other sleep researchers, may have given him the space to develop his ideas—while depriving him of resources at the same time.

  FIGURE 5.1. Bedřich Roth in 1959.

  Source: Courtesy of Jan Roth.

  FIRST ENCOUNTER WITH NARCOLEPSY IN PARIS

  The text of an autobiographical speech, provided by Roth’s son Jan, has a section titled “How I Came to Engage in Sleep Research.” Roth describes how he first observed someone with narcolepsy at the Salpêtrière hospital in Paris. He spent just two years in Paris, but the experience shaped the rest of his life.

  Some of Roth’s important learning experiences were in France. We can view him as being an extension of the French tradition of neurology, embodied by figures such as Charcot, Babinski, and Tourette. In particular, Charcot developed the Salpêtrière, once an insane asylum and prison for prostitutes, into a premier center for neurology in the late nineteenth century. He is also remembered for his discredited work on hypnosis and hysteria.3 Still, Charcot made detailed symptomatic and anatomical descriptions of several diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson’s, paving the way for them to be understood scientifically. Decades later, Roth undertook similar tasks for narcolepsy and IH.

  During his medical training, immediately after World War II, Roth spent time at a clinic supervised by the neurologists Pierre Mollaret and Georges Guillain. Every Tuesday at the hospital, professors examined outpatients in front of an auditorium of students. On one of those days, Mollaret brought in someone with narcolepsy. “All that the patient complained of was sleepiness, but, using precisely targeted questions, Prof. Mollaret was able to establish that the patient was also suffering from cataplexy,” Roth wrote. “I had great admiration for him then.”

  Mollaret, Roth’s primary teacher, was known for his studies of brain anatomy, as well as of infectious diseases such as malaria. During World War I, Guillain and his colleague Jean Barré had identified the autoimmune paralysis named for them (Guillain-Barré syndrome).4 Roth’s thesis was on polio and was titled “Considerations on the Prolonged Treatment of Respiratory Paralyses, with the Aid of an Iron Lung.” Roth was also involved in early efforts to treat Guillain-Barré syndrome with penicillin, according to his son.

  In 1949, after Roth had returned to Czechoslovakia, he began working at the Charles University neurology department, where two people with narcolepsy were being treated. One of them displayed “peculiar attacks lasting about 5 minutes.” These episodes sound like cataplexy, since the patient was unable to move or talk yet perceived what was going on around him. Roth’s colleagues thought the attacks were manifestations of hysteria, but he came to his own conclusion: it was a state of dissociation between body and mind, with the body entering sleep while the mind stayed awake.

  After studying the two people with narcolepsy, Roth had them come to a seminar, which was attended by neurologists and other physicians all over the country. Aware of his interest in such disorders, his colleagues began to refer patients with pathological sleepiness to see him. By 1952, he was able to report having seen forty-two patients with narcolepsy, all with cataplexy. Descriptions of hundreds more with narcolepsy and hypersomnia would follow. “He felt that he was part of the international community of sleep researchers and wanted to contribute to it,” his daughter Anniki Rothova said. “He didn’t have access to the same equipment or resources, but what he did have was a unique group of patients.”

  Roth established one of the first clinics devoted to sleep disorders, beginning in the early 1950s, before many others in Europe or the United States.5 Roth was a master of EEG interpretation, capable of diagnosing narcolepsy by glancing at a patient’s EEG recordings. However, most of his recordings came from daytime naps, since Roth didn’t have technical staff, like in a modern sleep lab, to help him observe someone progressing through the cycles of nighttime sleep.

  The Charles University neurology department was housed in a former monastery, which was reconstructed in the eighteenth century and then converted into an asylum for the mentally ill. In 2017, Roth’s former student Karel Šonka showed a group of visitors a now-unused section of the building, with small, cramped rooms where Roth had conducted sleep studies. Those that work in the rest of the building today say its appearance hasn’t changed much in years.

  To Šonka, who was much younger, Roth had “a quiet charisma.” Roth’s friends and family remember a gentle, gregarious man who almost never raised his voice. According to his daughter, he had a subtle sense of humor, playing with language, inventing new words and prodding his family to look at situations in new ways. He would buy sweets for colleagues from a shop across the street when one of his papers was accepted by an international journal.

  ESCAPE FROM RUZOMBEROK

  Outwardly mild-mannered, Bedřich Roth displayed determination and improvisation as a young man during the wartime occupation of his country. He was born in 1919 in Ruzomberok, a town in central Slovakia. His family was Jewish, observing religious holidays and dietary restrictions. His father Moritz was a lawyer, but the family was not well-off. When the elder Roth died in 1930, from complications after gastric surgery, his wife, Elsa, had to start working as a dressmaker.

  In Ruzomberok, the close-knit Jewish community had a synagogue and cemetery, a kosher butcher and a separate school. Many young people, including Roth, were part of Jewish sports clubs and summer camps. Roth loved to hike and ski in the nearby Tatra Mountains, and this affinity stayed with him his entire life.

  In the fall of 1937, Roth began his medical studies at Charles University. A year and a half later, Nazi Germany invaded and absorbed the western part of Czechoslovakia. In the separate German-allied state of Slovakia, Jewish students were barred from attending universities. After student demonstrations against occupation, Charles University was closed until the end of the war.

  Back in his home town, Roth found a job in a locksmith’s shop. In the evenings, he continued to study medical textbooks borrowed from the local hospital. He appears to have narrowly missed being deported to a concentration camp. He and other young Jewish and Roma men were called up for military service, which for them meant hard labor on tasks such as road repair. The first transports from Slovakia to Poland occurred in March 1942.6 A second round occurred in May. Most of Bedřich Roth’s extended family was eventually killed, according to his son.

  Despite Ruzomberok’s small size, the town was home to a textile plant and paper mills. Roth deserted from military service to make his way back to Ruzomberok, where shipments of lumber were being sent by train to Switzerland. A friend who worked at a sawmill learned the train schedules and bribed the man loading them to prepare a wagon with enough space to hide inside. In August 1942, Bedrich Roth and his cousin Jozef smuggled themselves by train all the way through Austria, ending up in Switzerland. It was an uncomfortable, cramped journey lasting more than a week. The cousins had to stay silent to avoid military guards along the way.

  The cousins were first taken to a Swiss prison, then a refugee camp and a labor camp. After several weeks, they were able to contact a representative of the Allied-backed Czechoslovakian government-in-exile in Switzerland. Roth managed to spend two years in Bern continuing his medical studies. As the Nazis’ grip on Europe loosened, he made his way to France, hoping to join the Czechoslovak armed forces.

  Roth arrived in Paris at the end of 1944, just a few months after that city’s liberation from its German occupiers. He spent several days on the cold streets, sleeping in Metro stations, after he did not pass an examination needed for military service. A sympathetic diplomat at the Czechoslovakian embassy helped arrange for a scholarship, allowing Roth to finish his medical studies in France. Roth’s training with Mollaret took place in postoccupation Paris, when many buildings had been demolished or lacked heat, and food was scarce. Part of the Pitié-Salpêtrière hospital complex had been taken over successively by the German and then American militaries.7

  Roth returned to Czechoslovakia at a tumultuous time, as the Communist Party was preparing to take power. People with his background and wartime experiences faced suspicions. Roth joined the Party in 1948, at a time when many academics and professionals were being recruited.8 Roth’s son said his father’s affiliation reflected his genuine sympathies, although he had been to France and Switzerland and saw through Communist propaganda.

  At Charles University, Roth had an ally in Kamil Henner, chairman of neurology, who shielded him from political trouble and encouraged his research interests. In his early work, Roth used a Grass EEG machine, then state of the art, obtained with Henner’s help from UN relief funds.9

  SLEEP DRUNKENNESS

  A man Roth first met in 1950, a nurse with the initials DV, made an impression on him.10 As a child, DV had experienced infectious hepatitis and stomach problems and suffered daily headaches as a teenager. At age twenty-five, he was well known to his family and coworkers for difficulty waking up. Positioning alarm clocks close to DV’s head or banging on a door didn’t do the job. “The only way to wake up the patient is by shaking him fiercely,” Roth wrote. “This usually makes him partially awake; he usually says something, but then he sleeps on. He must be shaken ceaselessly and dealt with resolutely, until he finally gets up.”

  Even when DV did get dressed and eat, he did so like an automaton, and when he arrived at work thirty minutes later his coworkers would notice how drowsy he appeared. During his military service, he was often punished for being late to morning lineup. Three years later, DV was working in a hospital, spending nights on the same corridor as several doctors. They were often awakened by his “special English alarm clock” ringing five times in a row, which DV slept through.

  Despite this man’s difficulties waking up, he was slow to fall asleep in the evenings and did not doze off against his will during the day. Paradoxically, staying up late seemed to help him. Thus, he had difficulty transitioning out of sleep, but his total level of sleep demand, in terms of hours per week, wasn’t as strong as in other patients Roth had seen.

  DV appears in Roth’s 1956 paper on sleep drunkenness, which focused on twenty patients, eleven of whom had an independent form of the condition and nine others who experienced it together with narcolepsy or epilepsy. In this paper, he laid out the concept that sleep drunkenness is at one end of a spectrum of sleep disorders, with narcolepsy with cataplexy at the other end. Sleep drunkenness was both a symptom that could appear in other disorders and the marker of a separate entity. The English summary concluded that sleep drunkenness “may appear either in an independent form or within the framework of the narcoleptic syndrome.… In the idiopathic forms it is a case of functional insufficiency with at present no demonstrable organic basis, most probably congenital or acquired at an early stage.”

  Roth was not the first to use the term “sleep drunkenness”; he cites a 1905 paper from the German psychiatrist Hans Gudden; the German word is Schlaftrunkenheit. However, Gudden was writing about a different situation, when someone is awakened from deep sleep. Today, sleep specialists would term this sporadic, acute state “confusional arousal,” in contrast with the chronic symptom that Roth observed in some of his patients.

  GENETICS AND DEPRESSION

  A family also appears in the 1956 paper on sleep drunkenness: a mother, two children, and the mother’s sister. The mother, a medical student, first came to him at age thirty-three; the trigger of her hypersomnia’s onset was mysterious. She would fall asleep while typing and often sleep more than fourteen hours in a day. After waking up, she was disoriented and said she felt as if she had just emerged from anesthesia.

  For her depression, the mother was treated with electroshock therapy in Prague. The depression receded, but her sleep disorder persisted for years afterward. The mother’s two children both had similar symptoms; one was the locksmith in training from chapter 1. Roth points out that in the older siblings, the illness appeared in their thirties, accompanied by depression, while in the second generation, it appeared around puberty, but without depression.

  Genetics emerged as a theme later in Roth’s work with his colleague Soňa Nevšímalová. She began working with Roth in the 1960s, quizzing patients about the content of their dreams and conducting neuropsychological examinations. She went on to become a respected clinician and researcher in her own right, studying hereditary neuropathies and neurodegenerative diseases. “It was largely because of Bedřich Roth’s influence that I began studying sleep,” Nevšímalová said in an interview in her office, where she still kept charts of patients they had seen together.

  In the early 1970s, Nevšímalová completed her PhD thesis in genetics, compiling histories and pedigrees of patients with narcolepsy and hypersomnia. She found that patients with IH frequently had relatives with the same condition—more than a third did. The effect was stronger when sleep drunkenness was present. Nevšímalová described two families in which three successive generations developed what she called “essential hypersomnia of the sleep drunkenness type,” later named idiopathic hypersomnia. One forty-year-old man could not hear alarm clocks, was disoriented upon waking for thirty to sixty minutes, and often slept for several hours in the afternoons. His mother and teenaged daughter had similar symptoms.11

  Because of the strong inheritance pattern, Nevšímalová and Roth believed that hypersomnia might be determined by a mutation in a single gene, inherited in a dominant fashion but with incomplete penetrance, not always manifesting in disease.12 The pattern contrasted to postencephalitic or post-traumatic cases of hypersomnia. Before recombinant DNA and sequencing technology was available, it was not possible to pin down what genes were responsible or determine whether the same gene was mutated in separate families.

  Nevšímalová and Roth observed a high rate (26 percent) of depression in people with IH.13 A similar number (28 percent) of those with narcolepsy without cataplexy also had depression. At that time in Czechoslovakia, people were less likely to consult a psychiatrist than people in Western Europe or the United States. Depression was a relatively rare diagnosis; its prevalence was estimated at around 1 percent, and depression was generally defined as requiring hospitalization or involving a suicide attempt. Nevšímalová and Roth remarked: “Some of the depressive symptoms might, of course, be due to the inability to cope because of daytime somnolence rather than being a symptom of the same basic neurochemical disturbance.”

  In some patients, worsening depression went together with stronger hypersomnia, so they were thought to be both features of the same disturbance. Antidepressants presented a puzzle; they didn’t alleviate sleepiness in narcolepsy, but they could diminish abnormal sleep states if someone had hypersomnia connected with depression.

  Roth himself suffered from bouts of depression for around thirty years and was treated with the tricyclic antidepressant amitriptyline, according to his children. “My father would be the first person to say that his decisions were influenced by depression,” his daughter said. “When he was in such a state, all sorts of emotions would be amplified—guilt, his sense of being attacked or perceived fault. But when he was free of depression, he was full of jokes and smiles.”