Narcolepsy – causes, symptoms, diagnosis, treatment & pathology

At one time or another you’ve probably had
to force yourself to stay awake, maybe while driving or when you’re in a looong lecture. In these situations, you were exerting control
over your sleep-wake cycles. Narcolepsy is a disorder in which individuals
lose the ability to regulate these sleep-wake cycles, so the normal boundary between sleeping
and being awake is blurred, and that leads to characteristics of sleeping happening while
a person is awake. In the brain, there are a special group of
neurons that help increase the state of wakefulness, and they extend from the lateral hypothalamus
to various parts of the brain like the reticular activating system (or RAS). In individuals with narcolepsy, there are
fewer of these excitatory neurons, and each neuron carries less of the neuropeptides orexin
A and B (also called hypocretin 1 and hypocretin 2). These orexins increasing the activity of wake-promoting
regions of the brain, thereby tipping the scales in favor of wakefulness and preventing
inappropriate transitions into a sleeping state. with narcolepsy, it’s thought that an autoimmune
process might damage the neurons delivering orexin or that there may be some other direct
injury to those neurons. Either way, when that happens, less orexin
is sent out and sleep-related symptoms begin to intrude into wakefulness. The onset of narcolepsy often happens during
adolescence and young adulthood, and is classically associated with four key symptoms. The first is daytime sleepiness, where people
chronically feel sleepy. They can get sleep attacks where they doze
off with little warning, sometimes inappropriately, but they generally don’t sleep more than
healthy people in a given 24 hour period. Most individuals with narcolepsy find that
a short, 15-minute nap substantially improves their alertness for a few hours, which suggests
that the sleepiness of narcolepsy is caused by a problem with the brain circuits that
normally promote full alertness, rather than poor quality or insufficient sleep. Normally when a healthy person goes to bed,
they go through a sleep cycle lasting an hour or more before they reach REM sleep, which
is the stage of sleep that is characterized by dreaming. People with narcolepsy fall asleep very quickly,
in as little as five minutes, and they often go directly into REM sleep. This results in their having very vivid dreams,
even when they fall asleep for brief periods of time. Alright the second symptom that often develops
over time is cataplexy which is when some strong emotion, which can be a positive one
like laughter or a negative one like anger, triggers a transient muscle weakness. That muscle weakness is often partial, affecting
the face, neck, and knees, but severe episodes can cause total body weakness or paralysis,
causing the person to collapse. These people are usually conscious during
cataplexy, and the weakness they feel usually resolves within minutes. Understandably, this symptom can have a severe
impact on the lives of people with narcolepsy, both from a physical (since they could get
hurt when they collapse) as well as a psychological perspective. The fear of cataplexy and having an episode
in public can lead to extreme anxiety, and will often lead to these people to avoid situations
that they believe might elicit an episode. The third symptom is having hypnagogic hallucinations
which are vivid, often frightening visual, tactile, or auditory hallucinations that occur
as the patient is falling asleep. They probably result from a mixture of wakefulness
and the dreaming of REM sleep. Hypnopompic hallucinations are similar except
that they occur upon awakening; although these are less common, they can happen in narcolepsy. Okay so the final key symptom is sleep paralysis,
which is the complete inability to move for a few moments to a few minutes immediately
after awakening or just before falling asleep. This is because during REM sleep the brain
is very active, but the voluntary muscles of the body are generally paralyzed, probably
to prevent an injury related to a dream about running or flying. This paralysis generally subsides as we start
to wake up, but occasionally we regain consciousness before the paralysis has worn off. Episodes of sleep paralysis can be even more
frightening because the immobility might be accompanied by hypnopompic hallucinations
or a sensation of suffocation. Interestingly, only a minority of people with
narcolepsy experience all four symptoms, which can make diagnosis difficult or make it easy
to get confused with other sleeping disorders. Evaluations like polysomnography or a multiple
sleep latency test, both of which take physiologic measurements like EEG and ECG tracings, while
a person is sleeping, can be used to help diagnose narcolepsy. For treatment, while there is no cure for
narcolepsy, there are a number of medications including specific stimulants and antidepressants
that can be used to help manage many of the symptoms. Alright, so to recap, in narcolepsy there
is a lack of orexin which is a neuropeptide that normally helps maintain a state of wakefulness. In its absence, many phenomena normally associated
with sleep begin to affect the waking state causing symptoms like daytime sleepiness,
cataplexy, hypnagogic hallucinations, and sleep paralysis. Thanks for watching, you can help support
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