Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Narcolepsy

What is Narcolepsy?

• Narcolepsy is a rare, chronic, debilitating neurologic disease of sleep-wake state instability that impacts approximately one in 2,000 Americans. It is characterized by excessive daytime sleepiness (EDS) and elements of rapid eye movement (REM) sleep (e.g., cataplexy, sleep paralysis, hallucinations) intruding into wakefulness.
• Narcolepsy often takes years to recognize in patients. Narcolepsy is diagnosed through a sleep study, a set of medical tests including an overnight Polysomnogram (PSG) and a Multiple Sleep Latency Test (MSLT)
• While the cause of narcolepsy is not completely understood, current research points to a combination of genetic and environmental factors that influence the immune system.
• It is best to be under the care of a physician who is specially trained, Certified in Sleep Medicine, Board Certified in Neurology, and experienced in treating Narcolepsy.
• Narcolepsy affects 1 in 2,000 people – over 200,000 Americans and 3 million people worldwide. In other parts of the world such as Japan, Narcolepsy appears as frequently as 1 in every 500. Narcolepsy is not rare, but it is severely under-recognized and commonly misdiagnosed.​
• People are not born with Narcolepsy. Generally, symptoms become apparent before early adulthood with children as young as three years old having been diagnosed.
• Narcolepsy affects both males and females equally and appears throughout the world.
• People with narcolepsy are more likely to be overweight. The weight gain may be related to medications, inactivity, binge eating, hypocretin deficiency, or a combination of factors​​
• There are two types: Narcolepsy with Cataplexy (N+C) and Narcolepsy without Cataplexy (N-C).
  • Cataplexy in narcolepsy is the weakening of muscles when you feel strong emotions like embarrassment, laughter, surprise, or anger
  • Cataplexy can cause your head to drop, your face to droop, your jaw to weaken, or make your knees give way. These attacks can also affect your whole body and cause you to fall
  • Not everyone with narcolepsy has cataplexy, but cataplexy could be a sign of narcolepsy

How Do You Get It?

• In N+C, an autoimmune reaction destroys the brain’s 70,000 hypocretin-producing cells. Hypocretin neurotransmitters are essential to proper regulation of sleep and wakefulness.
• The cause(s) of N-C are not well understood.
• Narcolepsy may have several causes. Narcolepsy is almost always linked to the lack of a neurotransmitter called hypocretin, or orexin. Neurotransmitters are brain chemicals that neurons produce to communicate with each other and to regulate biological processes. Loss of hypocretin results in the inability to regulate sleep.​
• The reason for such cell loss remains unknown, but appears to be autoimmune in nature. The body’s immune system selectively attacks hypocretin-containing brain cells. In rare cases, Narcolepsy is caused by a genetic defect that prevents normal production of hypocretin.
• Recent research points to two infectious agents that may be involved in triggering the condition
• Frequently, Narcolepsy onset follows a seasonal pattern of higher rates in spring and early summer, following winter upper airway infection season.
• Researchers are investigating a possible link between narcolepsy and streptococcus infection
• The current understanding of narcolepsy is that it begins with an underlying genetic predisposition; a person is born with pre-existing genes that put them at a greater risk
• In the child or teen years, an event such as infection may trigger the onset of narcolepsy.
  • Instead of the immune system simply attacking the infection, it becomes confused and attacks the specialized cells in the brain that produce hypocretin. The loss of hypocretin-producing cells leads to the symptoms of narcolepsy. Because the immune system is believed to be responsible for the loss of these cells, narcolepsy is considered an autoimmune disease. One of the triggering events linked to narcolepsy is an infection of the H1N1 influenza virus.​
• Researchers think that certain factors may work together to cause a lack of hypocretin. These factors may include:
  • Heredity. Some people may inherit a gene that affects hypocretin. Up to 10 percent of people who have narcolepsy report having a relative who has the same symptoms.​
  • Infections​
  • Brain injuries caused by conditions such as brain tumors, strokes, or trauma (for example, car accidents or military-related wounds).​
  • Autoimmune disorders. With these disorders, the body’s immune system mistakenly attacks the body’s cells and tissues. An example of an autoimmune disorder is rheumatoid arthritis.​
  • Low levels of histamine, a substance in the blood that promotes wakefulness.​

What Are The Symptoms?

• Symptoms usually begin during the teen or young adult years. The disorder also can develop later in life or in children, but it’s rare before age 5.​
• Not everyone with Narcolepsy experiences all of the symptoms nor to the same degree. Severe symptoms do have the potential to impact lifestyle quality similar to that of Parkinson’s or Epilepsy.​
• Excessive Daytime Sleepiness (EDS), an overwhelming sense of tiredness and fatigue throughout the day​
• Poor quality of sleep because the sleep wake patterns are disrupted​
• Micro-naps (falling asleep for a few seconds) and sleep attacks (an overwhelming urge to sleep)​
• Abnormal REM sleep, detectable only by sleep lab tests​
• REM intrusion into daytime wakefulness​
• Cataplexy​
• Hypnogogic hallucinations, events of vivid audio and visual events that a person with narcolepsy experiences while falling asleep, or while awakening
  • People with narcolepsy can have vivid, dream-like hallucinations while falling asleep or as they are waking up. During these episodes, the visions feel real—for example, seeing a person in the bedroom. The hallucinations are called hypnagogic if they happen while falling asleep, and hypnopompic if they happen while waking up.​
  • At the same time, people with narcolepsy experience paralysis as they’re falling asleep or waking up. This is the normal muscle paralysis associated with rapid eye movement (REM) sleep, but occurring at the wrong time. Although the paralysis usually only lasts a few seconds, it can be very frightening, especially in combination with hallucinations.​
  • Hallucinations and paralysis are caused by a disrupted boundary between dream sleep and wakefulness. Rather than gradually reaching REM sleep at the end of a sleep cycle, a person with narcolepsy can enter REM immediately. This means the dreaming and muscle paralysis of REM will occur directly from a waking state. Like sleepiness, these symptoms can sometimes be seen in those without narcolepsy, too.​​
• Sleep paralysis, a limpness in the body associated with REM sleep resulting in temporary paralysis when the individual is falling asleep, or awakening​
• At various times throughout the day, people with Narcolepsy experience irresistible and sudden bouts of sleep, which can last from a few seconds to several minutes. This sleepiness is similar to how non-narcoleptics feel when going without sleep for 48-72 hours.​
• Sleep episodes can occur at any time: at work or school, during a conversation, playing a game, eating a meal, or most dangerously, when driving an automobile or operating other types of machinery.
• The normal process of falling asleep begins with a phase called non-rapid eye movement (NREM) sleep. During this phase, your brain waves slow considerably. After an hour or so of NREM sleep, your brain activity changes, and REM sleep begins. Most dreaming occurs during REM sleep.​
  • In narcolepsy, however, you may suddenly enter into REM sleep without first experiencing NREM sleep, both at night and during the day. Some of the characteristics of REM sleep, such as cataplexy, sleep paralysis and hallucinations, occur during wakefulness or drowsiness in people with narcolepsy.​

How Is It Treated?

• In most cases of Narcolepsy the special cells in the brain that produce Hypocretin (Orexin) die. Hypocretin is important for regulating the Sleep/Wake Cycle and cannot yet be safely replaced. Because of this, the only way to treat Narcolepsy is to relieve the symptoms.​
• Narcolepsy is a life-long disease. The symptoms may vary in severity during the patient’s lifespan, but they never disappear completely. Symptoms usually gradually worsen over time, and then tend to become stable.​
• A primary care physician, usually in collaboration with a sleep medicine specialist, can recognize the symptoms of narcolepsy, initiate the proper evaluation, and manage the treatment that is recommended by the specialist.​
• Medications to relieve Excessive Daytime Sleepiness (EDS):
  • ​Sodium Oxybate (XYREM®), also FDA-approved for reducing cataplexy
  • Wakefulness Promoting Medications including Modafinil (Provigil®) and Armodafinil (Nuvigil®)
  • Central Nervous System Stimulants such as Methylphenidate (Ritalin®, Ritalin SR®, Methylin®, Methylin ER®), Mixed Amphetamine Salts (Adderall IR®, Adderall XR®), Dextroamphetamine (Dexedrine®, Dexedrine SR®), and Lisdexamfetamine (Vyvanse®)
• ​Medications to Reduce Cataplexy (partial of full muscle weakness) and other REM Sleep Disturbances:
  • Sodium Oxybate (XYREM®), also FDA-approved for reducing EDS​
  • Antidepressants that repress REM Sleep, such as:​
    • Serotonin Norepinephrine Reuptake Inhibitors like Venlafaxine (EffexorSR®)​
    • Norepinephrine Reuptake Inhibitors like Atomoxetine (Strattera®)​
    • Selective Serotonin Reuptake Inhibitors like Fluoxetine (Prozac®) and Sertraline (Zoloft®)​
    • Older Tricyclic Antidepressants like Protriptyline (Triptil® and Vivactil®), Imipramine (Janimine® and Tofranil®), Desipramine (Norpramine® and Pertofran®), and Clomipramine (Anafranil®)​
• Behavioral approaches include establishing a regular, structured sleep-wake schedule. Planned naps of 15 to 30 minutes or longer may be beneficial in reducing daytime sleepiness. Certain dietary restrictions should be observed (for example, avoidance of large meals and alcohol). Regular exercise and exposure to bright light can improve alertness. Occupational, marriage, and family counseling may help improve the patient’s quality of life.
  • Follow a regular sleep schedule. Go to bed and wake up at the same time every day.​
  • Do something relaxing before bedtime, such as taking a warm bath.​
  • Keep your bedroom or sleep area quiet, comfortable, dark, and free from distractions, such as a TV or computer.​
  • Allow yourself about 20 minutes to fall asleep or fall back asleep after waking up. After that, get up and do something relaxing (like reading) until you get sleepy.
  • Certain activities, foods, and drinks before bedtime can keep you awake. Try to follow these guidelines:​
    • Exercise regularly, but not within 3 hours of bedtime.​
    • Avoid tobacco, alcohol, chocolate, and drinks that contain caffeine for several hours before bedtime.​
    • Avoid large meals and beverages just before bedtime.​
    • Avoid bright lights before bedtime.​
• Special considerations may be needed for school schedules and working conditions. Occupations that require working in shifts, changing the work schedule, or driving should be avoided. The dangers of driving while sleepy and/or experiencing cataplexy need to be addressed and the patients should be advised to avoid driving with these symptoms. However, many patients with narcolepsy are able to drive for short distances at certain times of the day and after taking their stimulant medications. Reporting requirements to the Department of Motor Vehicles (DMV) differ from state to state​
• There are many specialties of doctors a person with narcolepsy might consult for treatment, including:​
  • A primary care physician (such as a general practitioner, family practitioner, internal medicine specialist, and a pediatrician): This is usually the primary health care professional.​
  • Neurologist: This is a physician who treats disorders of the brain, spinal cord, and nerves.​
  • Sleep medicine specialist: This is often a neurologist or pulmonologist, but can be another qualified doctor.​
  • Psychiatrist: This is a physician who specializes in the treatment of mental, emotional, and addition disorders.​

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this illness from the Narcolepsy Network.