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Understanding Narcolepsy


This short video shows narcolepsy in canines. The disorder has been observed in research in mice, rats, dogs, and horses. Although these cases develop with slight deviations from the human form, they are instructive for better comprehending the overall causes, symptoms, and treatments.

But one research tool in narcolepsy is particularly exciting because it could affect the clinical analysis of the disorder in the near future. Traditionally, narcolepsy is observed in animals and human patients by connecting electroencephalogram (EEG) electrodes to the individual’s skull. Using a monitor, a researcher may examine the different brain waves and when they occur. On the EEG recordings, narcolepsy appears as long strands of rapid eye movement (REM) brain activity that is not preceded by deep slow-wave sleep. (Narcolepsy pertains to problems in REM sleep. A narcoleptic patient falls abruptly into REM sleep while he is awake.)

In animals, such as mice, observing narcolepsy can be time-consuming and difficult because of the tiny electrodes that must be implanted in the skull without damaging any of the disorder’s physiological manifestations. The process for classifying sleep stages is also laborious, especially since a researcher must manually read through the squiggly array of brain wave activity in order to correct any classification errors conducted by the computer software.

Fortunately, there may be a solution to these problems because the jagged REM brain waves are not the only way to ascertain a period of narcolepsy. The piezoelectric (PZT) system has long been known for its environment-promoting technology in converting vibrations into electrical energy. Recently, the sensory device has diversified its uses as researchers experiment with it for analyzing sleep disorders such as narcolepsy. Future endeavors pertaining to PZT may not only boost animal safety but even accelerate studies on sleep.

More specifically, because the PZT monitor discerns motion, it can potentially be used as a noninvasive method for observing cataplexy in narcoleptic experimental animals such as mice. Recent studies demonstrate the PZT’s ability to record the animal’s heart and respiration rates as it is lying down. The device consists of a metal platform with sensors. When a narcoleptic mouse has a bout of cataplexy, it collapses and lies flaccidly against the platform. The PZT sensors, aligned beneath the surface, then detect the mouse’s heart rate and record it. These sensors can potentially discern between a normal resting period and a real case of cataplexy within the mouse due to differentiations between the two heart rates. While the invasive EEG relies on brain activity and algorithms to classify the mouse’s sleep stages, the passive PZT may more accurately catalog instances of cataplexy, which could revolutionize research in narcolepsy for all mice, experimenters, and human patients (Sagawa et al.).

PZT is now only tested on mice and may help in animal experiments for trialing narcolepsy treatments in the future. However, it may soon replace the EEG methods of recording human brain activity. Perhaps someday, researchers will attach a small PZT monitor to the narcoleptic patient’s chest in a far simpler manner of observing the disorder in humans.

Despite recent advances, narcolepsy has only recently become a cutting-edge frontier in sleep research. It was first described in medical literature in 1877, and it now only appears in 0.05% of the world population. Therefore, it is no surprise that its causes and cures are still hazy (Mignot).

It is specifically a sleep disorder characterized by an individual’s distorted circadian rhythm and short bouts of paralysis and hallucinations. The patient displays excessive daytime sleepiness (EDS) in the form of sleep attacks, in which he feels a strong urge to take a short nap during the day. Insomnia consequently occurs at night. As implied by the PZT experiments, cataplexy is also a common symptom of narcolepsy. It consists of abrupt periods of muscle weakness or paralysis effected by extreme feelings of positive emotions (such as excitement or surprise). Such periods of cataplexy may last anywhere from a few seconds to one minute (Montagna and Chokroverty 119).

Narcolepsy also has slighter symptoms that may be discerned only by the patient. A narcoleptic often has sleep paralysis, in which he may be paralyzed at the onset of sleep, during a short moment of wakefulness at night, or upon awakening in the morning. During these moments of paralysis, he may have extreme frightening hallucinations that will only terminate by some external stimulus. At the physiological level, narcoleptics may have a lower blood pressure and body temperature. They are almost always obese although they ingest less food than normal (Montagna and Chokroverty 121).

Evidently, at the neuronal level, there must be a multitude of dysfunctions for so many threatening symptoms to occur at once. Yet this point is also where narcolepsy faces resistance because of crucial knowledge that current researchers lack. Scientists know that the disorder revolves around the neurotransmitter orexin (also called hypocretin), which regulates feeding and sleep. Narcolepsy occurs when there are low or no levels of orexin being circulated through the brain (Mignot).

The orexinergic neurons based in the lateral hypothalamus deteriorate at some point during the narcoleptic individual’s life, which causes the onset of the disorder. Because of this abrupt neuronal apoptosis, narcolepsy is likely an autoimmune disease. However, more proof is required to confirm this belief. (Carlson 229).

Normally, the orexinergic neurons fire during an individual’s daytime period of wakefulness and vigilance. Such firing presumably promotes alertness. Thus, due to the fewer orexinergic neurons that fire in a narcoleptic brain, the patient feels less awake during the day. At night, although there is conclusively less stimulation promoting wakefulness, the orexinergic effects of wakefulness are produced. Further research is still required to fully comprehend the reasoning behind this phenomenon.

This piece of information proves interesting because of narcolepsy’s apparent dissonance with the circadian rhythm’s traditional response to day and night. When we travel across the world, our circadian rhythms reset and adjust to the time zone. For example, if we are in China, which is about 12 hours ahead of America, the morning light acts as a zeitgeber to reset our physiological sense of time. But a narcoleptic, who has bouts of sleepiness during the day and insomnia at night in America’s time zones, will adjust to the new time setting but presumably continuing to have bouts of sleepiness in the day and insomnia at night.

So could there possibly be more at hand other than dysfunctions pertaining to the orexinergic neurons? Perhaps the suprachiasmatic nucleus (SCN), the primary controller of the human biological clock located in the hypothalamus, is a contributing source to the problem. In a similar autoimmune disease, maybe the SCN fails as a cause or effect of the orexinergic neuronal deterioration.

Narcolepsy has encountered a variety of semi-effective treatments, but current research proves that there is great hope for the future. Currently, the most common treatment is modafinil, a wake-promoting stimulant that works against EDS. Altogether, researchers have been investigating antidepressant drugs that fight against the REM sleep problems of narcolepsy. Such drugs promote serotonin and norepinephrine activity in the brain and can reduce the dysfunctions behind cataplexy, sleep paralysis, and hypnagogic hallucinations (Carlson 219).

In recent years, narcolepsy treatments have branched beyond the scope of traditional drugs. One such undertaking is hypocretin replacement therapy, which—as the name suggests—would reduce sleepiness and cataplexy by increasing orexinergic levels in the brain. In the therapy, the patient would be administered orexin receptor agonists through cell or gene transplantation. The agonists would promote the orexinergic effects and thus increase physiological alertness. Testing for this therapy is currently taking place (Nishino et al. 217-8).

From its coinage in 1880 to its correlation with orexin deficiency in 2000, human understanding on narcolepsy has developed immensely in the past 150 years. The disorder initially faced many roadblocks due to its rareness and the researching world’s lack of knowledge on the subject. Fortunately, the latter half of the twentieth century has passed with an increased interest in narcolepsy along with a forefront of hypotheses and features to test and dissect in the future. The ensuing century will doubtlessly solve many of the questions behind narcolepsy, with more possibilities for preventing the disorder and learning more about the circadian rhythm in the process.

Carlson, Neil R. Foundations of Behavioral Neuroscience. 8th ed. 2006. Boston: Allyn & Bacon-Pearson, 2011. Print.

Mignot, Emmanuel. “History of Narcolepsy.” History – Center for Narcolepsy – Stanford University School of Medicine. Stanford School of Medicine, 2001. Web. 21 Apr. 2012. <http://med.stanford.edu/‌school/‌Psychiatry/‌narcolepsy/‌narcolepsyhistory.html&gt;.

Montagna, P, and S Chokroverty, eds. Handbook of Clinical Neurology. Vol. 99. 2011. N.p.: Elsevier B. V., 2011. Print. 3.

Nishino, S, et al. “Hypocretin /‌ orexin and narcolepsy: new basic and clinical insights.” Acta Physiologica 198 (2009): 209-22. PDF file.

Sagawa, Yohei, et al. “Noninvasive detection of sleep /‌ wake changes in orexin /‌ ataxin-3 transgenic mice across the disease onset.” N.d. Microsoft Office PowerPoint file.

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