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Bedřich Roth, His Life’s Work and the 35th anniversary of the book “Narcolepsy and Hypersomnia”

*First published September 2015

I would like to take this opportunity during Idiopathic Hypersomnia Awareness Week 2015 to acknowledge the 35th anniversary of the classic text Narcolepsy and Hypersomnia (1980 S. Karger; NY, NY) and to pay tribute to the extraordinary contribution to neurological sleep research by renowned neurologist Bedřich Roth.

The book Narcolepsy and Hypersomnia was published in English in 1980 and is an accumulation of Roth’s work spanning more than 30 years. In fact, it is officially Roth’s second monograph on narcolepsy and hypersomnia. The first volume was published 23 years earlier in 1957 - 'Narcolepsy and hypersomnia from the aspect of physiology of sleep' [1] making Roth’s work the first in the area of modern day era Narcolepsy and Hypersomnia research. So, it is difficult to celebrate the 35th anniversary of the publication of the book Narcolepsy and Hypersomnia without documenting the history that led up to the writing of it including the many significant contributions that Bedřich Roth made to sleep research.

Bedřich Roth Roth was a renowned neurologist responsible for identifying and naming Idiopathic Hypersomnia. His seminal works over many years on narcolepsy and idiopathic hypersomnia have left an indelible mark on the history of sleep medicine. Roth was born in Slovakia into a Jewish family on 23rd March 1919. In 1937 he started studying medicine in Prague Czechoslovakia. After the outbreak of World War II, he was detained for some time in a concentration camp in Slovakia where he was forced to do hard labour. Roth, fortunately, escaped the camp and fled to Switzerland where he resumed his medical studies. After the liberation of France, he made his way to Paris where he completed his medical degree in 1946. After a short time working in Paris, he returned to Czechoslovakia. Roth first worked in the neurology department at the hospital of Hradec Králové and then in 1949 he moved on to the Department of Neurology at Charles University. Despite the adversities of the political and economic situation at the time not experienced by western countries, Roth successfully developed the world’s first sleep laboratory. This is where he spent the next 40 years working as a physician, teacher and scientist until his death in 1989.

Early years 1950-59

Life in Communist-ruled Czechoslovakia during this time meant every aspect of Roth's work was made difficult. He received little funding, had few resources and even required permission from the Soviet-controlled government to attend congresses and meetings to present his findings and to participate in discussions with regards to his own work and that of others. Yet despite these extreme adversaries Roth is credited as being a true pioneer in the area of narcolepsy and hypersomnia due to the valuable epidemiological data he compiled on these disorders [2] Many of his peers regard the book Narcolepsy and Hypersomnia as a true “classic” [2,3]. Accomplished narcolepsy researcher Dr Mignot acknowledges that Roth is responsible for the first careful epidemiological studies of narcolepsy and idiopathic hypersomnia and that Roth's work led to the classic diagnostic "narcoleptic tetrad" ie: cataplexy, sleep paralysis, hypnagogic hallucinations, and excessive daytime sleepiness that is still used today [4].

In a discussion with Dr Roger Broughton while researching for this tribute he said that the book Narcolepsy and Hypersomnia “included not only his remarkable progress having worked on the topic for over a quarter of a century but also citation of the world-wide publications on these interesting diseases. Indeed, it made clear that Professor Roth was the first neurologist to specialise more or less exclusively in the area of narcolepsy and hypersomnia. The earliest contributors elsewhere came mainly from Stanford, California, Montpellier France and Bologna, Italy whose first publications were not until the early to mid-1960 ’s. Moreover, Professor Roth clinical experience in the field was vastly greater than that in these other centres. His case series of persons with narcolepsy and cataplexy and of others with symptomatic hypersomnia each ran into the many hundreds of patients a significant proportion of whom he had followed, often with Professor Nevismalova, for several decades. He also had a significant series of patients with idiopathic hypersomnia and a good number of others with recurrent hypersomnia (Klein-Levin syndrome, bipolar disorder and menstrual hypersomnia) which was also unique at the time of his book”.

Prior to Roth’s first monograph in 1957 his work included a number of studies

where he recognised and recorded the clinical differences between narcolepsy and hypersomnia [5,6,7,8,9,10]. This included an early very detailed article on the EEG in narcolepsy published in 1952 [5]. Sleep drunkenness, a typical feature of idiopathic hypersomnia was first recorded in his 1956 paper Sleep Drunkenness and Sleep Paralysis [9]. It was during this time that Roth started to realise that patients with hypersomnia but without the classic clinical features of narcolepsy and without any other explanation for their symptoms were suffering from an independent clinical entity.

Narkolepsie a Hypersomnie S. Hlediska Fysiologie Spanku – 1957

Years of careful and meticulous study of a large number of patients led to Roth’s first monograph; Narcolepsy and hypersomnia from the aspect of physiology of sleep (Narkolepsie a Hypersomnie S. Hlediska Fysiologie Spanku – 1957). This monograph was described in the book Sleepiness: Causes, Consequences and Treatment as “a master book” [11]. It is very significant as it documented the early work Roth had been doing almost exclusively over the previous six years identifying the very distinct differences between patients with narcolepsy and those with hypersomnia. The 1957 monograph was based upon a large number of personally observed cases. The series included 248 patients and proposed to differentiate patients with narcolepsy (155) from patients with hypersomnia (93). Roth identified several subgroups of patients. Among the narcoleptic patients, he distinguished patients with essential narcolepsy (194), including patients with narcolepsy with cataplexy (70) and patients with narcolepsy without cataplexy (34), from patients with symptomatic narcolepsy (51). Among the patients with hypersomnia, he separated those with functional hypersomnia including patients with neuroses (27) and patients with vegetative dystonia (23), patients with organic basis (29), and patients with independent post-dormital drunkenness (14) later referred to as the polysymptomatic form of idiopathic hypersomnia (1976).

1960’s and beyond

By now it was clear to Roth that the subgroups of hypersomnia patients including those with idiopathic hypersomnia did not have narcolepsy. This identification was later confirmed by other researchers including Dement in the 1966 paper “The nature of the narcoleptic sleep attack“ [12] “Subjects with excessive daytime sleepiness but no cataplexy, sleep paralysis or sleep onset REM periods do not have narcolepsy and should be relegated to another diagnostic category”.

Roth’s work during the 1960’s and 70’s included many great professional achievements and collaborations. In 1965 Roth presented one of the first papers written on the polygraphic study of narcolepsy and hypersomnia [13]. In 1969 Roth with Bruhova published a study on REM and NREM sleep in these disorders [14] and in the same year they published one of the first papers using polysomnogram focusing on dreams in narcolepsy and hypersomnia [15,16]. Another important study during this time was Roth’s first collaboration with Allan Rechtschaffen, Nocturnal sleep of hypersomniacs [17].

In 1967 Roth was invited to join a committee of investigators with experience in scoring sleep, led by Allan Rechtschaffen and Anthony Kales. The aim of the committee was to develop a terminology and scoring system to be universally used by sleep specialists. They developed the first consensus-based guidelines for staging and scoring sleep in human subjects, “A manual of standardised terminology, techniques and scoring system for sleep stages of human subjects” commonly called R&K or Rechtschaffen and Kales [18].

Roth continued to make significant contributions to sleep research throughout the 70’s and 80’s right up until the time of his death in 1989. In 1972 the European Sleep Research Society was established in Basel Switzerland where Roth was one of the founding members. Collaborations in 1972 and 73 with Nevšímalová resulted in papers on the familial tendency of narcolepsy and idiopathic hypersomnia. These papers were significant because up until this time a genetic connection had not been explored in these disorders [19,20]. Another collaboration with Allan Rechtschaffen, Hypersomnia with Sleep Drunkenness was published in 1972 [21]. Other collaborations resulted in further studies with PSG in narcolepsy and idiopathic hypersomnia [22] and investigations into the psychological and socioeconomic impact of idiopathic hypersomnia on the life of the patient were written with Broughton and Nevšímalová and published in 1975 and 1978 [23,24]. Roth’s most cited paper “Narcolepsy and hypersomnia: review and classification of 642 personally observed cases” was published in 1976 [25] and Idiopathic Hypersomnia: a study of 187 personally observed cases was published in 1978 [26]. Roth’s years of extensive research that led to his description of idiopathic hypersomnia as a separate disease entity was accepted and included in the first ICSD, Diagnostic Classification of Sleep and Arousal Disorders in 1979 [27]. As the world authority on idiopathic hypersomnia, Roth's work through the 70's and early 80's included writing papers, book chapters, collaborations, presenting papers and chairing workshops at international congresses with a particular focus on educating others on the clinical picture and definition of idiopathic hypersomnia [28,29,30].

In a fitting end to an outstanding body of work in 1986, Roth's group in collaboration with the Max Planck Institute in Germany was one of the first to discover an association between HLA DR2 and Narcolepsy [31].

After many requests from his peers to translate his 1957 monograph into English Roth spent a considerable amount of time with Roger Broughton writing Narcolepsy and Hypersomnia. The “blue book” as it was sometimes known was published in 1980 [32].

Narcolepsy and Hypersomnia (1980 S. Karger; NY, NY)

“Pathological states of inappropriate or excessive sleep – narcolepsy and hypersomnia – are very frequent and cause the afflicted subjects considerable inconvenience and distress. The study of these hitherto inadequately elucidated conditions can help us to a better understanding of them and thus lead to more accurate diagnosis and to more effective treatment. The clinical, electroencephalographic and polygraphic investigation of these syndromes can also furnish valuable information concerning the physiology of both sleep and wakefulness” Bedřich Roth – Preface, Narcolepsy and Hypersomnia 1980.

Roth also explains in the preface of Narcolepsy and Hypersomnia that “findings obtained in the initial 251 patients studied over a period of six years were summarized in a monograph entitled “Narcolepsy and hypersomnia from the aspect of physiology of sleep”, published in Czech in 1957, which contained extensive Russian and English summaries. A German translation was published in 1962. Although widely cited in international literature, the full text of this book was unfortunately inaccessible to readers not knowing Czech or German. Consequently, I was frequently asked by many colleagues to publish an English translation. During the past 20 years, however, there have been such scientific advances in the fields of the physiology and the pathology of sleep that it has proven necessary to rewrite the book in its entirety, I hesitated for a long time before deciding to do so, as I was well aware of the many difficulties involved. But I believe that the clinical experience acquired and the findings obtained during 26 years of systematic study of these problems could be of value to the medical and scientific public and so decided to proceed…”

The book Narcolepsy and Hypersomnia is based on 30 years of Roth’s work on these disorders including the data from his study published in 1976 [25]. This study included patients with either narcolepsy (368) or hypersomnia (274) that Roth personally examined and observed at the Charles University Neurology Clinic in Prague between 1949 and 1975. Many patients were studied for 15 to 20 years, some for as much as 25 years or more, all with meticulous follow up. Each patient was examined clinically and by EEG, many of them repeatedly and as of 1966 each of the patients was also examined via polysomnograph (PSG). This series of narcolepsy and hypersomnia patients remains the largest ever studied making Roth’s epidemiological studies on narcolepsy and idiopathic hypersomnia unsurpassed. It contributed to the literature the largest most meticulously followed series of all of the then known neurological sleep disorders and provided new information on the pathophysiology and genetics of these disorders [33].

Roth made significant contributions to the advancement of the modern day identification of narcolepsy. This is documented in various papers and publications including both of his monographs. For this tribute, we will be focusing primarily on the hypersomnias, in particular, idiopathic hypersomnia.

368 narcolepsy cases were classified according to their aetiology, clinical form and path physiological mechanisms of origin. The 274 hypersomnia cases were divided into symptomatic and functional groups and then further distinguished by "short cycle hypersomnia" and "long cycle hypersomnia”. Roth’s first task was “to distinguish the symptomatic hypersomnias determined by some known underlying disease or organic brain condition, or metabolic affection or intoxication from the functional hypersomnias, in which pathological sleep is not induced by other known disease” SYMPTOMATIC HYPERSOMNIA:

Of the 274 patients with hypersomnia 61 patients were identified as having hypersomnia caused by a known disease or medical condition. Roth noted that organic brain conditions including head trauma, bacterial and viral infections, vascular diseases and tumour were the most frequent causes of hypersomnia. And “amongst metabolic conditions, hepatic and renal diseases” were also common causes. Drugs and medications also “represented another frequent aetiology”. The clinical picture including the severity and intensity of the sleepiness in symptomatic hypersomnia varies depending on the underlying cause. “Sometimes sleepiness can be mild and the patient can easily be awakened…at other times his sleep may be very deep so that it is very difficult to wake him.” The course of hypersomnia also depends on the evolution of the underlying condition. “In favourable cases, the patient may recover and all the symptoms may disappear… Sometimes the underlying condition regresses, but irreversible changes have occurred in the brain which causes the hypersomnia to become chronic”.

FUNCTIONAL HYPERSOMNIA: The term “functional hypersomnia” includes the hypersomnias not caused by other sleep disorders or medical or mental disorders. Of the 213 patients with functional hypersomnia Roth further divided them into short cycle (191) and long cycle (22) functional hypersomnia. The difference in these cycles is the length of the sleep periods and the time between episodes. Long Cycle Functional Hypersomnia (periodic hypersomnia): Long cycle hypersomnia also referred to as periodic hypersomnia is comparably rare to the short cycle hypersomnias. Roth distinguished two forms of long cycle functional hypersomnia, monosymptomatic (15) and polysymptomatic (6). In both forms “..the condition is characterised by states of excessive sleep lasting from one day to several weeks” patients then usually experience periods where they are completely symptom free “lasting from one to several months or even years As a rule, the longer the duration of the attacks, the longer the intervals between them.” In the polysymptomatic form (Kleine- Levin Syndrome) periods of hypersomnia can also be “accompanied by polyphagia (excessive eating/increased appetite) and mental disturbances”. Various degrees of behavioural or cognitive disturbances and hypersexuality are also associated with this form of recurrent hypersomnia. Short Cycle Functional Hypersomnia: Short cycle functional hypersomnia is more common than long cycle. In Roth’s series, it included idiopathic hypersomnia (monosymptomatic 71 and polysymptomatic 103), neurotic hypersomnia (5) and hypersomnia associated with sleep apnea (12). Hypersomnia with sleep apnea: Unlike in patients with idiopathic hypersomnia where patients tend to have a greater capacity to stay awake despite usually constant excessive sleepiness Roth noted that patients with sleep apnea are usually unable to overcome sleepiness and as a result typically nod off frequently, often in inappropriate circumstances throughout the day. “Most patients are sleepy for a large portion of the day, and, in severe cases, for virtually the entire day. They are often unable to overcome their sleepiness and will fall asleep against their will, even in the most unsuitable situations. Patients in my own series have stated that they fell asleep while standing and walking, while eating or working, during conversation, while driving a car, in the toilet, and in other inappropriate circumstances. These episodes of excessive daytime sleep are usually of short duration (the patient sleeps only a few minutes), but their frequency is high, and short periods of sleep often alternate with equally short periods of wakefulness.” It was also noted that some patients have longer daytime sleep episodes of around 30-60 minutes. Duration of sleep over a 24 hour period is greater than normal however due to constant respiratory disturbances the sleep is light and non-restorative. Patients wake up feeling unrefreshed and morning headaches are common. Roth quoted several studies including one of his own that show sleep apnea also occurs in narcolepsy with cataplexy. Sleep apnea, however, does not occur in idiopathic hypersomnia. The concept of the CPAP (Continuous Positive Airway Pressure) machine was discovered by Australian respiratory physician, Colin Sullivan in June 1980 [34]. Since then various oral devices have also become available for the treatment of sleep apnea. Unfortunately, despite full compliance and effective treatment of apnea events with either CPAP or oral device sleep apnea patients can still experience excessive daytime sleepiness, this is referred to as “residual sleepiness” [35,36,37,38,39]. There are a number of possible causes for residual sleepiness including depression, obesity which in itself is associated with sleepiness and in some patients a natural vulnerability to sleep deprivation or sleep disturbance has also been found to contribute to residual sleepiness [35,36,38]​. Therefore despite effective treatment of apnea events a number of patients with treated sleep apnea may still experience what Roth described as “hypersomnia with sleep apnea”. It should also be noted that CPAP has limited effectiveness in reducing sleepiness in milder sleep apnea [39]. More awareness of this fact and of residual sleepiness is needed to prevent misdiagnosis of idiopathic hypersomnia in these patients. Idiopathic Hypersomnia: The clinical description and neurophysiological characterisation of idiopathic hypersomnia was made by Bedrich Roth in a series of papers published over the course or more than 30 years. The book Narcolepsy and Hypersomnia is an accumulation of all of that work which is why it was considered a valuable text by clinicians and scientists.“Study of the functional hypersomnia patients showed that over 80% presented a highly uniform clinical picture. These were all short cycle hypersomnia manifested by daily diurnal sleep episodes lasting up to several hours. The condition develops most often during puberty and then remains stationary. The symptoms are permanent. A large number of these patients have now been followed for 10 to 20 years or more. With my colleague Nevsimalova (Nevsimalova and Roth 1972, Nevsimalova 1973) we have found a heredofamilial pattern in over 30% of all cases. They represent an independent nosological entity, for which I have suggested the term “Idiopathic Hypersomnia” [27]. Roth identified two variants of Idiopathic Hypersomnia, a monosymptomatic and polysymptomatic form. In his series, the monosymptomatic form manifested in daytime hypersomnia alone. However, studies have shown that patients with monosymptomatic hypersomnia can also experience long nocturnal sleep. The polysymptomatic form also includes daytime hypersomnia. However, it’s most striking features are exceptionally deep and protracted (long) nocturnal sleep and sleep drunkenness on arousal. Patients with polysymptomatic hypersomnia can find it extremely difficult to wake from sleep. Sleep drunkenness was first identified by Roth in 1956, however, the most significant paper was published in 1972 [9,21]. Clinical picture: Excessive daytime and nocturnal sleep with significant daytime sleepiness are the major symptoms of idiopathic hypersomnia with sleep drunkenness and extreme difficulty waking from sleep typical in the polysymptomatic form. “The excessive daytime sleepiness is not as irresistible as it is in narcolepsy. The patient usually does not fall asleep against his will while engaged in some activity, and especially not in circumstances inappropriate for sleep such as during a conversation, while eating or while riding a bicycle. He is obliged, however, to fight sleepiness for a large part of the day and eventually must lie down and go to sleep; subjects may even fall asleep sitting up…As a rule, these patients are able to resist sleep for the whole of their working day. When they get home, however, they simply have to lie down and sleep. The duration of the periods of daytime sleep varies from about 30 minutes to as much as 5-8 hours. If the patient goes to sleep in the afternoon, he may not wake up again before the following morning. Some patients will even sleep for a whole weekend – from Friday afternoon until Monday morning – virtually without a break. In addition to attacks of excessive sleep, patients complain of long periods of intense sleepiness, which in some cases is more or less permanent.” “Excessive daytime and nocturnal sleep with significant daytime sleepiness are the major symptoms of idiopathic hypersomnia with sleep drunkenness typical in the polysymptomatic form. The excessive daytime sleepiness is not as irresistible as it is in narcolepsy. The patient usually does not fall asleep against his will while engaged in some activity, and especially not in circumstances inappropriate for sleep such as during a conversation, while eating or while riding a bicycle. He is obliged, however, to fight sleepiness for a large part of the day and eventually must lie down and go to sleep; subjects may even fall asleep sitting up…As a rule, these patients are able to resist sleep for the whole of their working day. When they get home, however, they simply, have to lie down and sleep. The duration of the periods of daytime sleep varies from about 30 minutes to as much as 5-8 hours. If the patient goes to sleep in the afternoon, he may not wake up again before the following morning. Some patients will even sleep for a whole weekend – from Friday afternoon until Monday morning – virtually without a break.”

Other clinical symptoms and signs; Roth noted that some of his patients had other symptoms as well as excessive sleep, sleepiness or sleep drunkenness. While none of these symptoms were attributed to the aetiology of idiopathic hypersomnia they would in most cases contribute to the burden of the disease. Studies show that patients with idiopathic hypersomnia become tired and sleepy in both over and under stimulating conditions “… given that the patients feel tired in the presence of over-stimulating conditions (a loud environment, strangers and flashing light), and feel sleepy in under-stimulating conditions (darkness, left alone or listening to a conversation). Basically, it appears in this study that the patients would feel all right only during holidays, in a nice landscape with sun and friends. One may wonder if they use, in this case, the motivation ⁄ mood system to stay awake rather than the usual arousal systems” [40]. This would suggest if patients are constantly relying on their motivation/mood system to stay awake rather than the usual arousal systems then depression, anxiety and associated psychological difficulties including irritability, emotional and mental lability and fatigability would be an obvious consequence. Nocturnal sleep: The majority of patients nocturnal sleep onset was noted as being usually extremely quick “often within a few seconds” with only a small number reporting difficulties falling asleep. The majority of Roth’s patients also reported sleeping “very well and deeply”. Some patients likened their sleep to being unconscious. Many patients also claimed to either not dream at all or only very rarely. Nocturnal sleep as with daytime naps is most often unrefreshing. “An extraordinarily deep and often also prolonged night sleep is reported especially by those patients who suffer from sleep drunkenness upon awakening. If allowed to sleep until spontaneous awakening they often sleep 12 or even 20 hours or even more without awakening” Subsequent studies done by other groups confirm that Polysomnogram (PSG) shows sleep of normal quality with few awakenings and a normal proportion of the different sleep stages. Sleep apneas, restless legs, and periodic movements in sleep are absent [41]. Sleep Drunkenness: Sleep drunkenness consists of difficulty in coming to complete wakefulness accompanied by confusion, disorientation, poor motor coordination, slowness, and repeated returns to sleep. Patients report that these symptoms occur at almost every awakening; nearly all report abnormally "deep" and prolonged sleep as well. “Patients rarely waken spontaneously at an appropriate time; they have to be awakened. They usually do not awaken to the ringing of a clock or telephone, or, if the ringing is prolonged, they shut it off and return to sleep. Many patients have special devices for waking them up such as repeating alarm clocks and resonators. In most cases, these devices are ineffective, and the patients have to be awakened by their family members. Awakening procedures must be vigorous and persistent; it is usually necessary to shake the patient repeatedly before he reacts. Even then the patients are confused, disoriented, very slow, and unable to react adequately to external stimuli. If left alone, they often return to sleep and later do not remember having been previously awakened.” [21] Roth’s observations of sleep drunkenness in a subgroup of patients with idiopathic hypersomnia have been confirmed in subsequent studies by other researchers. Sleep drunkenness has been noted as being highly specific to idiopathic hypersomnia as clear-cut sleep drunkenness is not found in the general population [40,42]. Regular healthy people or people with other medical conditions including other sleep disorders may experience either fairly regular or from time to time a mild sleep inertia or they may feel groggy for a while after waking up however that is not considered sleep drunkenness in the context that it has been identified in patients with polysymptomatic idiopathic hypersomnia. Sleep drunkenness is recognised as a significant disability in the daily life of patients [40]. Extreme difficulty awakening from sleep: Patients with idiopathic hypersomnia particularly those with the polysymptomatic form find it extremely difficult to awaken from sleep. As mentioned above if patients are allowed to sleep until they wake spontaneously they can sleep 12 or even 20 hours or more without awakening. Sometimes patients can attempt to wake up after 12 or 14 hours with no success. They may very briefly (often while their eyes remain closed) try to wake up several times before eventually spontaneously awakening many hours later at which time they will still experience sleep drunkenness. This extreme difficulty awakening from sleep followed by sleep drunkenness usually happens every time a patient goes to sleep ie: after nighttime sleep and daytime naps. The sleep is also often completely unrefreshing “Subjects affected with this type of idiopathic hypersomnia often refrain from naps because of their spontaneous long duration and their unrefreshing nature.” [41] EEG & Polysomnographic (PSG) Findings: EEG findings in idiopathic hypersomnia were described in a number of papers [5,8]. With regards to the 167 idiopathic hypersomnia patients examined and referenced in Narcolepsy and Hypersomnia, there were 134 recordings with an “incidence of sleep patterns”, only 10.2% were completely normal. With regards to the daytime sleep features in idiopathic hypersomnia during polygraphic studies sleep patterns were found in 85.1% of all recordings and “in all cases NREM sleep was ascertained. Deep stages of NREM sleep (stages 3 and 4) were found relatively frequently.” The nocturnal sleep of these patients was also studied. The sleep was found “to be completely normal apart from its long duration (12 hours and more). The percentages of REM and NREM sleep were normal, as was the periodicity of the sleep cycles, the number of which was simply increased.” [17] Differential Diagnosis: Roth noted that the differential diagnosis of idiopathic hypersomnia includes, other sleep disorders including, narcolepsy and sleep apnea, symptomatic hypersomnia (hypersomnia caused by another disease or disorder), and neurotic hypersomnia. Roth also explained the importance of distinguishing the difference between “sleep drunkenness of a sporadic nature from idiopathic hypersomnia with sleep drunkenness”. Also, “sleep drunkenness can occur from time to time in anyone who is awakened after inadequate sleep, in strange surroundings or after taking a sedative, a hypnotic or alcohol. It also characterises nocturnal awakenings in sleepwalkers who are notoriously deep sleepers…. However, in polysymptomatic idiopathic hypersomnia, sleep drunkenness occurs every day..” Billiard has studied idiopathic hypersomnia extensively over many years, during Roth’s time and up to the present day. He has written a number of papers based on his studies. In a 1996 paper Billiard wrote; “Indeed, in the author's experience, idiopathic hypersomnia is one of the most overdiagnosed sleep disorders because there is a tendency to classify in this category all hypersomnias that do not fit the criteria of either narcolepsy or the sleep apnea syndrome.” [41] Billiard noted that the complaints of patients with a number of conditions are similar to those of patients with idiopathic hypersomnia and should be considered. These include upper airway resistance syndrome, hypersomnia associated with dysthymia and related mood disorders, chronic fatigue syndrome, hypersomnia that develops after a viral infection, such as atypical viral pneumonia, mononucleosis, or Guillain-Barre syndrome etc, post-traumatic hypersomnia, delayed sleep phase syndrome, pain or other medical symptoms responsible for fragmented sleep at night frequently result in excessive daytime sleepiness and of course, insufficient sleep and poor sleep hygiene. An important consideration that is sometimes missed is “long sleepers”, also called "healthy hypersomniacs are persons who require more sleep at night than the norm. They may be misdiagnosed with idiopathic hypersomnia because of extremely long sleep episodes at night. These subjects are normally alert, however, once they have obtained their needed amount of sleep.”

Another reason for misdiagnosed cases of idiopathic hypersomnia is due to the current diagnostic methods. “The diagnostic value of the MSLT is somewhat questionable in subjects with the polysymptomatic form of idiopathic hypersomnia, however. In these cases, awakening the subject early in the morning for the MSLT precludes documentation of the prolonged nighttime sleep, and the MSLT protocol precludes the recording and observation of prolonged, unrefreshing daytime sleep episodes. Thus, it is more useful to perform an all-night sleep polygraphic recording followed by an MSLT and then, from 7:00 PM onward, a 24-hour continuous polysomnography, either at home with an ambulatory system or in the laboratory on an ad lib protocol.” [41]

Idiopathic Hypersomnia - What do we know now?

Compared to the advances in narcolepsy research there has unfortunately not been a lot of meaningful progress made with idiopathic hypersomnia. This is due to several reasons. One issue is that the MSLT was considered the ‘gold standard' with regards to diagnosing idiopathic hypersomnia and narcolepsy, however, research has shown not only it's inadequacy in diagnosing idiopathic hypersomnia and narcolepsy without cataplexy (now known as narcolepsy type 2 [N2]) but also its inability to accurately distinguish N2 from idiopathic hypersomnia [44,45,46,47].

Consequently, a lot of the work that has been done has not advanced the epidemiological, etiological or pathophysiological understanding of idiopathic hypersomnia thus our knowledge has not moved on much further from what we have learned from Bedrich Roth’s original work.

Research into narcolepsy has come a long way since Roth’s early narcolepsy epidemiology studies. With the discovery of hypocretin/orexin deficiency being unique in narcolepsy with cataplexy (now known as narcolepsy type 1 [N1]) [48,49] we now know that Roth’s very early observations were accurate in that N1 and idiopathic hypersomnia are separate clinical entities. Roth also noted that N2 was more similar to what he described as monosymptomatic hypersomnia (referred to in the ICSD-2 as idiopathic hypersomnia without long sleep [IH w/o LST]) than it is to N1. This too has been confirmed by further research [42,52,53].

Therefore, what we know clearly shows that idiopathic hypersomnia is not a variant of Narcolepsy. While the division of idiopathic hypersomnia into with and without long sleep may not be accurate, research suggests that there is more than one form of idiopathic hypersomnia [42,43,50] or perhaps that idiopathic hypersomnia is a spectrum disorder that encompasses N2 [47]. Following the latest classification of idiopathic hypersomnia in the ICSD-3, it was felt that idiopathic hypersomnia had been "defined negatively against narcolepsy and secondary and comorbid hypersomnias and encompasses perhaps a variety of different diseases” [51]. This led Karel Šonka and Michel Billiard to perform a detailed cluster analysis [42]. The analysis included subjects with idiopathic hypersomnia and narcolepsy with and without cataplexy. The analysis found that there were 3 distinct and separate clinical entities.

Cluster 1 – “Combined monosymptomatic hypersomnia/ narcolepsy type 2”

(23 cases of IH w/o LST, 19 cases of N w/o C and two cases of IH with LST)

Cluster 2 – “Polysymptomatic hypersomnia”

(24 cases of IH with LST, two cases of IH w/o LST and one case of N w/o C)

Cluster 3 – Narcolepsy type 1

(23 cases of N with C)

*IH w/o LST = idiopathic hypersomnia without long sleep time, IH with LST = idiopathic hypersomnia with long sleep time, N w/o C = narcolepsy without cataplexy, N with C = narcolepsy with cataplexy.

The study also discussed the spectra of narcolepsy and idiopathic hypersomnia; “The important contribution of this work lays in the confirmation that cluster narcolepsy type 1 (former N with C) and cluster polysymptomatic hyperso