Discussing The Narcolepsy Condition, Its Signs and Symptoms

“I’ve heard that sometimes a version of you must die before another more enlightened version can be born. I think that’s true after watching the corpse of myself walk around.”

Introduction

With over seven billion humans in the world, it is clear that human experience is a relatively independent and unique thing. However, there are some aspects of being human – or even being alive – that tie people and animals alike. The need to breathe, sleep, eat, and propagate the species transcends time, culture and even taxonomic diversity. With this in mind, some processes make for an interesting study in how both animals and humans function. Related to this, the phenomenon of narcolepsy in living beings – humans and animals alike – makes for a unique study in biological and circadian processes. Simply put, narcolepsy is the phenomenon of sleepiness during the day, cataplexy, and other related symptoms like fragmented sleep. There has been a great deal of research conducted on this topic, so the knowledge surround narcolepsy – its characterizations, symptoms, diagnosis, and physiology – is well established. This discussion paper examines narcolepsy both in general and in terms of three specific models of narcolepsy and how it manifests. First, the paper turns to an overview of narcolepsy, including its symptoms, diagnosis, and physiology. Second, the paper discusses narcolepsy in animals; this second section deals primarily with rats and mice. Third, the paper examines narcolepsy in relation to the circadian rhythm, and asks whether narcolepsy occurs equally during the day as it does at night. Finally, the paper discusses the role of emotion in narcolepsy, and what types of emotional feelings can act as trigger events for a narcoleptic attack. While this discussion is not exhaustive, examining these various aspects of scientific knowledge surrounding narcolepsy will go a long way toward establishing an understanding of the phenomenon.

Basics of Narcolepsy

First, the overall discussion will benefit by turning to an overview of what narcolepsy is in scientific terms and how it functions. As noted above, narcolepsy is characterized by various symptoms, such as “excessive daytime sleepiness, cataplexy, [and] fragmented sleep” (Baumann, Bassetti, & Scammell, 2011, 5). In simple terms, cataplexy is a medical condition that causes individuals to collapse (though remain conscious) after the onset of a very strong emotion or the physical response of this emotion, such as laughter (Baumann, Bassetti, & Scammell, 2011, 5). As will be discussed, because of the confluence of both cataplexy and fragmented sleep, these two symptoms are thought to be indicators (if not preexisting conditions) of narcolepsy. However, the jury is still out on this front. As the authors quoted above go on to state, “The prevalence of narcolepsy without cataplexy is largely unknown, as a proper population-based study would require an MSLT of all subjects”; however, in case studies, they also note that narcolepsy patients without cataplexy represent anywhere form 20%-50% of all cases of narcolepsy. Clearly, though there is some conception of the connection between cataplexy and narcolepsy, the scientific knowledge so far has not made a direct link between the two types of symptoms.

This is despite the fact that scientists have been studying narcolepsy for well over a century. As Baumann, Bassetti, & Scammell (2011) note, “until recently, its cause remained a mystery” (5). The largest breakthrough was in 2000, when two independent research groups discovered the physiological cause of narcolepsy: “a selective loss of neurons in the hypothalamus that produce the hypocretin neuropetides (also known as orexins)” (Baumann, Bassetti, & Scammell, 2011, 5). In other words, narcolepsy is caused not be a chemical imbalance or chemical response, but by the preexisting setup of the neurons within an individual’s brain. It was with this “groundbreaking perspective” that “narcolepsy research has advanced in large steps, with new discoveries every year that have enhanced our understanding of the disorder” (Baumann, Bassetti, & Scammell, 2011, 6). Despite these steps forward, the main research question that remains is in regards to what ‘kills’ these neurons that cause narcolepsy in the first place.

But what is the consequence of narcolepsy? One of the main symptoms of narcolepsy is that it has “its major onset in adolescence” and often worsens with “puberty onset” with the main experience for early onset patients as having non-refreshing sleep (Wehrle & Bruck, 2011, 32). The consequence of this timeline is social as much as psychological: “The widespread and often severe psychosocial effects partially arose from a delay in diagnosis. Sever educational failure was a common consequence. Symptoms affected work and life goals. Increased social withdrawal and lower self esteem were often evidence. Sleepiness was a problem both for public transportation and driving, substantially affecting independent mobility” (Wehrle & Bruck, 2011, 32). With this in mind, it is clear that the scientific knowledge surrounding narcolepsy should be increased in order to better the recognition of the condition. As the authors go on to state, “Increased awareness of the disease and the provision of psychoeducational support, in conjunction with early diagnosis and medical treatment, are strongly warranted to prevent the most common educational and psychosocial problems, including risk of depression” (Wehrle & Bruck, 2011, 32). This is confirmed by another academic article, which also notes the occurrence rate of narcolepsy: it “occurs in approximately 1 in 2000 individuals, and usually begins in the teens and early twenties” with a lifetime prevalence of 1 to 18 for every 1000 people (Kishi, et al., 2004, 117; Ohayon et al., 2002). These two academic sources clarify that while there is a great deal of knowledge regarding narcolepsy, scientists are constantly learning more. The three specific models of narcolepsy discussed below should show how this knowledge is growing, and what it means for narcoleptic patients.

Narcolepsy in Animals

First of all, examining narcolepsy in animals is a good first step in building knowledge about the phenomenon. The prevalence and symptoms of narcolepsy in animals can go a long way toward building scientific knowledge regarding narcolepsy in humans. As one source states, “To facilitate further research, it is imperative that researchers reach a consensus concerning the evaluation of narcoleptic behavioral and EEG phenomenology in these models” – including animal models (Chen, Brown, McKenna & McCarley, 2009, 296). In order to approach this, the authors examine various models of narcolepsy. The first is in domestic animals like sheep, horses, dogs and even bulls (Chen, Brown, McKenna & McCarley, 2009). The authors focus on canines as a primary source of information for narcolepsy, since dogs have the largest rate of narcolepsy, particularly with cataplexy (Chen, Brown, McKenna & McCarley, 2009). The authors have specific insight regarding the canine model of narcolepsy: “Pedigree analysis indicated an autosomal recessive mode of transmission with full penetrance…it became clear that there are both familial and sporadic forms of canine narcolepsy” (Chen, Brown, McKenna & McCarley, 2009, 297). This insight provides one of the first steps toward understanding not only why narcolepsy occurs, but why there is a shortage of the necessary neurons in the hippocampus in the first place – that is, genetic mutation. However, the authors clarify that “it should be noted that genetic mutation alone may not account for the full symptomatic development of narcolepsy”, since those canines treated with anti-inflammatory agents at an early age reduced both cataplexy and narcolepsy (Chen, Brown, McKenna & McCarley, 2009, 297). The authors also delve into specific environments and triggers that can lead to the onset of narcolepsy in animal models. For instance, the authors found that there were three distinct stages of cataplexy in canines: “The initial stage had muscle atonia, waking-like EEG and visual tracking…The second stage resembled REM sleep with hippocampal theta activity…The final stage was characterized by EEG with mixed frequency and amplitude before a transition into wakefulness or sleep” (Chen, Brown, McKenna & McCarley, 2009, 298). These canine models are a good beginning for researchers.

A good resource for research on narcolepsy are rodent models of the phenomenon. According to one study, episodes of narcolepsy in mice were characterized by the following psymptoms: “the abrupt cessation of purposeful motor activity associated with a sudden, sustained change in posture that was maintained throughout the episode, ending abruptly with complete resumption of purposeful motor activity” (Chen, Brown, McKenna & McCarley, 2009, 301). The account of these symptoms, combined with a consideration of what activities and events preceded the attacks, help form a scientific idea of how narcolepsy occurs and what can precipitate narcoleptic attacks. It also helps understand how and when narcoleptic patients return to a normal state of either wakefulness or sleep after a narcoleptic attack and how long they can last.

Another study examined a more specific aspect of the animal model of narcolepsy: how genes impact the prevalence and symptoms of narcolepsy. This is actually one of the original studies that showed the importance of neurons and genes in causing narcolepsy in both animals and humans. As these authors state, “We report that a null mutation induced by targeted disruption of the mouse orexin gene results in an autosomal recessive phenotype with characteristics remarkably similar to narcolepsy” (Chemelli et al., 1999, 437). In other words, the authors found that the occurrence of narcolepsy in mice was directly related to a specific type of gene – or neuron. As the authors conclude, “These observations firmly identify orexins as neuropeptides with an important function in sleep regulation” (Chemelli et al., 1999, 437). This study, then, establishes the specific type of neuron, orexin, as the primary factor affecting narcolepsy.

Narcolepsy & Circadian Rhythms

The other topic that provides some insight into how narcolepsy functions is in relation to circadian rhythms. The main question here is whether narcolepsy is related to circadian rhythms; in other words, does narcolepsy occur more during the daytime, at night, or equally at all hours of the day? Because this is more easily observable than other aspects of narcolepsy, there is a great deal of knowledge on the topic. In regards to sleep and circadian rhythms overall, there is one source that is worth quoting at length:

“A series of findings over the past decade has begun to identify the brain circuitry and neurotransmitters that regulate our daily cycles of sleep and wakefulness. The latter depends on a network of cell groups that activate the thalamus and the cerebral cortex. A key switch in the hypothalamus shuts off this arousal system during sleep. Other hypothalamic neurons stabilize the switch, and their absence results in inappropriate switching of behavioral states, such as occurs in narcolepsy” (Saper, Scammell, & Lu, 2005, 1257).

In other words, narcolepsy is directly impacted not so much by a human’s internal circadian rhythm, but instead more by the internal processes of the hypothalamus. This is confirmed by another source, which states that “The mechanisms that potentially disturb the circadian rhythm of leptin levels in hypocretin-deficient narcoleptic humans include anomalies of the sleep-wake cycle and/or disruption of the circadian distribution of autonomic activity” (Kok et al., 2001, 8246). In other words, the neurological process that affects narcoleptic humans is completely independent from the circadian rhythm. This is confirmed again by a third study, which found that “the homeostatic process of sleep regulation is intact in narcoleptics…it appears that the circadian clock itself is functioning normally in narcoleptics” (Dantz, Edgar, & Derment, 1994, 24). With this in mind, one can safely conclude that narcoleptic attacks are just as likely to occur during the daytime as at night, since narcolepsy is not directly impacted by the circadian rhythm.

Narcolepsy & Emotion (1)

The last topic relevant to understanding narcolepsy in both human and animal models is how narcoleptic attacks relate to emotional feelings. First and foremost, it is clear that emotion has some part to play in narcoleptic attacks; for instance, one study found that “Emotions were found more often and were more intense in narcoleptic SOREM than in nighttime REM of either narcoleptic or normal subjects, with anxiety/fear exhibiting the strongest increase, followed by joy/elation” (Fosse, Stickgold & Hobson, 2002, 724). In this regard, SOREM refers to REM that occurs at the first stage of daytime naps and nighttime sleep (Fosse, Stickgold & Hobson, 2002, 724). This finding makes it clear that extreme emotions of both varieties – both positive and negative – can have a role in the onset and length of narcoleptic attacks, at least once sleep is already underway. As these authors conclude, “The REM sleep of patients with narcolepsy affords a unique opportunity to study emotion and to analyze its psychophysiology,” and their study found that “Narcolepsy intensifies REM-dream emotion, especially anxiety/fear and joy/elation, and this is most clearly seen during SOREM sleep” (Fosse, Stickgold & Hobson, 2002, 724). In other words, emotions can trigger narcoleptic attacks even during sleep. But what about emotional triggers while patients are awake, that result in cataplexy – which in turn results in narcolepsy? One study provides insight into this question, stating that “Cataplexy is one of the most intriguing examples of how thought content can alter neurologic functioning,” since patients in a state of cataplexy that also experience “an intense emotional state triggers objective transient muscle weakness verified by areflexia” (Krahn et al., 2005, 45). More specifically, the study identified the specific type of emotional response that serves as a primary trigger for cataplexy: laughter. As the authors report, “Patients with narcolepsy-cataplexy identified laughter as a more consistent cause of cataplexy than other closely related positive emotional states such as hearing a joke, feeling excited, feeling elevated, remembering a happy moment, or experience an (unspecified) emotional event” (Krahn et al., 2005, 47). Since cataplexy is closely related to the onset of a narcoleptic attack, the discussion here can conclude as well that these emotional responses are just some emotional feelings and stimuli that can bring on a narcoleptic attack.

Conclusion

This discussion paper has examined narcolepsy in four parts: first, as it relates to humans overall, second, as it relates to animal models, third, as it relates to circadian patterns and, fourth, as it relates to emotional feelings and related trigger events. While the discussion was certainly not exhaustive, the paper has made two insights clear. The first insight is that research has yielded a great deal of knowledge regarding narcolepsy, its symptoms, and even its causes. As the research presented above shows, much of the physiology of narcolepsy is already known. However, the discussion paper has also made another insight clear: that a great deal of research is missing in order to adequately understand not only how and why narcolepsy occurs, but how to prevent it. Clearly, understanding the processes and factors that can be affected by human intervention is the next (and most important) stage of research.