What are the other Names for this Condition? (Also known as/Synonyms)

• Gelineau's Syndrome
• Narcolepsy with Cataplexy
• Paroxysmal Sleep

What is Narcolepsy? (Definition/Background Information)

• Narcolepsy is a neurological disorder affecting sleep and wakefulness patterns. It is reported worldwide, without any gender, racial, ethnic or geographic bias
• The disorder may be characterized by extreme sleepiness during daytime, muscle weakness or lack of control over one’s muscles, hallucinations, and sleep paralysis
• Narcolepsy is caused by a deficiency of the neurotransmitter hypocretin, resulting from a combination of genetic and environmental factors
• Sporadic mutation(s) in the HLA family of genes, as well as other genes of the immune system, have been reported in individuals with Narcolepsy
• The diagnosis of the condition is made on the basis of characteristic symptoms, sleep studies, and measurement of hypocretin in the spinal fluid
• Presently, there is no treatment available to cure Narcolepsy. Medications, such as stimulants and anti-depressants, and psychological counseling may be required to manage the disorder
• The condition persists lifelong, but is often manageable with early diagnosis and prompt treatment. Most individuals are able to have a normal quality of life

Who gets Narcolepsy? (Age and Sex Distribution)

• Narcolepsy affects individuals worldwide; a frequency of approximately 25-50 cases per 100,000 individuals is noted
• The condition typically begins in the teens and early twenties, but can occur as early as five years, or even after the age of 40 years
• Although both sexes are affected, males are marginally more prone to this disorder than females
• No geographic, racial, or ethnic bias is generally observed

What are the Risk Factors for Narcolepsy? (Predisposing Factors)

The following are some known risk factors for developing Narcolepsy:

• A family history of the disorder
• A decrease in the levels of histamine in blood
• Certain infections (such as due to exposure to H1N1 swine flu virus)
• Brain injuries due to disorders, disease, or trauma
• Autoimmune disorders
• Exposure to environmental toxins, such as heavy metals, second-hand smoke, and pesticides
• Use of over-the-counter drugs that causes drowsiness can increase one’s risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Narcolepsy? (Etiology)

Narcolepsy is caused by the deficiency of hypocretins (also known as orexins). Hypocretins (hypocretin 1 and hypocretin 2) are neurotransmitters in the brain. It is produced by a small number of nerve cells in the region of the brain, known as the hypothalamus.

• Under normal circumstances, these neuropeptides are released during wakefulness
• However, in some individuals, the nerve cells producing hypocretin may be destroyed, leading to a deficiency in hypocretins, causing sleepiness and dysfunctional rapid eye movement (REM) sleep

The death of hypocretin-producing nerve cells can occur due to a combination of factors, many of them involving the immune system and contributing to the deficiency of the neurotransmitter. For this reason, Narcolepsy is often considered to be an autoimmune disorder.

The factors leading to a deficiency in hypocretin may include:

• Genetic predisposition:
  • It occurs with the inheritance of a variant of the gene (HLA) DQB1, known as the (HLA) DQB1*06:02
  • The (HLA) DQB1 gene belongs to the human leukocyte antigen complex and codes for the human leukocyte antigen. The HLA protein plays an important role in the immune response
  • It has been observed that individuals with this variant gene exhibit an increased susceptibility to Narcolepsy
  • Variants of other HLA genes (HLA-DQA1, HLA-DQB1, HLA-DRB1) and some additional gene’ variants, all involved in immune function (TNF, TNFRSF1B, TRA, CHKB, CPT1B), have also been reported
• Autoimmune disorders, such as rheumatoid arthritis
• Trauma to the brain
• Brain tumor
• Exposure to toxic chemicals

Most variations in genes involved in Narcolepsy arise sporadically. In instances where the condition runs in the family, no clear pattern of inheritance is discernable.

What are the Signs and Symptoms of Narcolepsy?

The signs and symptoms of Narcolepsy are as follow:

• Severe daytime sleepiness - this could be brief, lasting only for a few minutes
• Hallucinations - usually occurring at the onset of sleep, these can be vivid, and occasionally continue briefly, even when the individual wakes up
• Sleep paralysis: It refers to a weakness during sleep, which may persist briefly upon waking up, and can be mistaken for paralysis
• Cataplexy: It is the sudden onset of muscle weakness and loss of control of voluntary movement (although the individual is fully conscious), which may be triggered by factors such as:
  • Laughter
  • Crying
  • Being scared
• Cataplexy can lead to severe and generalized loss of muscle tone causing buckling of knees. It can make the individual prone to falls (risk of fall injuries)
• Insomnia
• Behavioral issues, such as compulsive smoking at night

How is Narcolepsy Diagnosed?

The diagnosis of Narcolepsy is made based on the following tests and exams:

• A thorough physical examination and an assessment of symptoms
• The following should be present for the healthcare provider to suspect the disorder:
  • Excessive daytime sleepiness (EDS)
  • Disrupted nighttime sleep
  • The above symptoms, with or without REM sleep dissociation, characterized by cataplexy, hallucinations, or sleep paralysis
• An evaluation of personal and family medical history
• Sleep study (polysomnography)
• Multiple sleep latency test (MSLT), typically undertaken the day following sleep study
• Measurement of hypocretin levels in the spinal fluid (CSF)
• Neurologic exam to elicit features supporting the diagnosis and to exclude other causes of sleepiness (such as insufficient sleep or sleep apnea)
• Magnetic resonance imaging (MRI) of the brain to rule-out (rare) brain tumors, if necessary
• Genetic molecular testing of HLA genes may help in understanding if the individual is predisposed to Narcolepsy

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Narcolepsy?

Narcolepsy can lead to complications such as the following:

• Being misunderstood as “being rude” when one falls asleep during meetings and conferences 
• Susceptibility to accidents while driving, which are known to be fatal
• Being labeled “lazy”
• Poor performance at school or workplace
• Withdrawal from emotional interactions for fear of loss of muscle control
• Anxiety and depression

How is Narcolepsy Treated?

Presently, there is no treatment to cure Narcolepsy. However, medications and lifestyle modifications can help an individual manage the symptoms effectively.

The following treatment methods are considered for this sleep disorder:

• Use of specific, prescribed stimulants such as:
  • Modafinil, which provides good control of sleepiness and is generally well tolerated
  • Methylphenidate, a potent wakefulness-promoting drug. Although effective, it is considered a second-line agent because of its side effects (such as increased heart rate, panic, heart failure and psychosis)
• Selective serotonin re-uptake inhibitors (SSRIs) for anxiety and depression
• Psychiatric counseling and group therapy
• Support of family and friends is beneficial

How can Narcolepsy be Prevented?

Currently, there are no guidelines or methods available for the prevention of Narcolepsy. However, the following factors may be considered:

• Undertaking prompt and adequate treatment of infections, such as caused by H1N1, and autoimmune disorders
• Avoiding exposure to environmental chemicals and pollutants
• Avoiding smoking or second-hand smoke
• If an individual suspect that he/she may have the condition, it may be helpful to avoid over-the-counter medications that cause drowsiness
• Routine physical examinations may be helpful in early diagnosis and efficient management of the condition

Research is ongoing for a better understanding of the genetics and physiology of Narcolepsy.

What is the Prognosis of Narcolepsy? (Outcomes/Resolutions)

The prognosis of Narcolepsy is determined by the severity of its signs and symptoms.

• Typically, the condition is not progressive, but it can persist for the duration of one’s life
• The symptoms can worsen during the first few years and may then stabilize
• A timely diagnosis and efficient management can help individuals lead as normal a life as possible

Additional and Relevant Useful Information for Narcolepsy:

In Narcolepsy, the affected individual usually feels rested after a nap, unlike those with sleep apnea, when one does not feel rested after a nap.