Narcolepsy

• What is Narcolepsy
• Statistics on Narcolepsy
• Risk Factors for Narcolepsy
• Progression of Narcolepsy
• Symptoms of Narcolepsy
• Clinical Examination of Narcolepsy
• How is Narcolepsy Diagnosed?
• Prognosis of Narcolepsy
• How is Narcolepsy Treated?
• Narcolepsy References

What is Narcolepsy

Narcolepsy is a disorder of the body’s normal sleep wake cycles, causing inappropriate sleepiness at unpredictable times during the day. Patients who suffer from narcolepsy may fall asleep at various times during the day, sometimes with little or no warning. The condition is characterised by four main symptoms.
These include (listed in decreasing frequency):

• Excessive / increased sleepiness during the day.
• Cataplexy (abrupt loss of muscle tone for a brief, temporary period of time, commonly triggered by sudden emotional reactions such as laughing or fear. This can cause symptoms such as weakness of the body, or inability to speak properly, to complete collapse of the body).
• Hallucinations – these are often visual disturbances that seem to resemble lifelike situations and circumstances, commonly indistinguishable from the real thing. Hallucinations are experienced commonly when the patient is falling asleep or waking up.
• Sleep paralysis – inability to move parts of the body when waking asleep or falling asleep. This may last for a few seconds to a few minutes and may be quite frightening for the person.

Actions such as automatic behaviour may occur – a person may continue to perform tasks such as putting things away during episodes of sleep. They commonly have no memory of performing these tasks. People who suffer from narcolepsy also experience interrupted sleep patterns at night.
Narcolepsy is thought to be due to a disruption of the normal boundaries between sleep and wake cycles. Normally, an average night’s sleep is about eight hours. This consists of five to six sleep cycles. One sleep cycle consists of a period of non rapid eye movement (NREM), followed by a period of rapid eye movement (REM). It is during the period of rapid eye movement sleep that you often experience dreams. A sleep cycle often lasts about 100-110 minutes, starting with NREM sleep and moving on to REM sleep after a period of approximately 80-100 minutes. People who suffer from narcolepsy enter REM sleep more quickly, often within a few minutes of getting to sleep.

Statistics on Narcolepsy

Narcolepsy is seen in many ethnic and racial groups around the world, affecting both males and females on a similar basis. Different prevalence rates are present in different populations. The condition is thought to be rare in the general population, but most rates are based on clinical samples that do not reflect the wider community.
According to various studies that have been performed, the prevalence varies as follows:

• 20-67/100,000 in Europe and North America
• 590/100,000 in Japan
• 1-40/100,000 in Hong Kong
• 40/100,000 in Saudi Arabia
• 0.23/100,000 in Jews in Israel

However none of these previous studies have been performed assessing the diagnostic elements of narcolepsy (e.g. the four main symptoms as discussed above). Based on a more recent study published in 2002 approximately 18,980 randomly selected patients were interviewed between 1994 and 1997. These patients were representative of the general population in the UK, Germany, Italy, Portugal, and Spain. Using different criteria for severity of disease from the International Classification of Sleep Disorders, the prevalence of narcolepsy ranges from between 26 and 47 individuals per 100,000. Narcolepsy was also found to be as frequently seen in men as in women, and not related to age. These findings are consistent with previous studies.
More than 50% of people with narcolepsy have experienced symptoms during their childhood and adolescent years. Often narcolepsy affects people between the ages of 15 – 30.

Risk Factors for Narcolepsy

Most cases of narcolepsy occur without any prior family history of the condition. However, a family history of narcolepsy has been reported in 6% to 40% of narcoleptic patients. The risk for narcolepsy is estimated to be 10 to 40 times higher among first degree relatives of narcoleptic individuals than in the general population. First degree relatives refers to people such as your mother or father, brothers or sisters.
The HLA complex has been strongly linked to narcolepsy. This complex refers to a number of gene forms located in a specific region of one of our chromosomes – chromosome 6. Greater than 90% of people who have narcolepsy have specific subtypes and variants of the HLA genes. Although these genetic factors may predispose some people to develop narcolepsy, other factors are also important in causing the disorder. Not all patients who have narcolepsy have these genes, and some people in the population have these genes do not have narcolepsy.
In addition to genetic factors, it is thought that there are often other predisposing factors such as infection, trauma and hormonal imbalances.
Narcolepsy has been shown to be due to a loss of substances in the nervous system called orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2). These substances excite specific nerve cells via special receptors. They are released when we are awake, increasing the activity of many brain regions involved in the promotion of wakefulness. This prevents inappropriate transitions during our sleep cycle. The loss of substances like orexin leads to elements of REM sleep intruding into times when we are awake (e.g. resulting in hallucinations, sleep paralysis).
Specific loss of the nerve cells in the brain producing orexin could also be found in people with narcolepsy, or these nerve cells could also be damaged. This may be due to an autoimmune or degenerative process. However, there is little evidence to support this.

Progression of Narcolepsy

The most commonly experienced symptom in people who suffer from narcolepsy is unexpectedly falling asleep during the day. These sleep disturbances tend to begin subtly but may change over time. Attacks often occur with little warning, at inappropriate times. This can result in serious consequences for the affected person – for example, narcolepsy can cause you to fall asleep when driving, or operating heavy machinery. This can result in significant consequences for yourself and other involved parties. Narcolepsy can also cause you to fall asleep during leisure activities (e.g. swimming, jogging) and during work. This occurs regardless of whether you get enough sleep at night. You may also feel tired during the day, lacking energy and suffer from a low mood. Inability to concentrate properly and impaired memory have also been reported by some patients.
Sleep episodes may last from a few seconds to many minutes. Sleep episodes can reoccur within the next one – two hours. Often, patients will wake up from the period of sleep feeling refreshed for the next couple of hours, but eventually tire and may fall asleep again. Some people may not actually fall asleep, but struggle with extreme sleepiness throughout the day.
The next most commonly experienced symptom is cataplexy, occurring in about 70% of patients. Cataplexy is the sudden, uncontrollable loss of muscle tone, leading to weakness and loss of control of muscles. Episodes can occur at any time during the day. Most patients experience cataplexy a few weeks or months after the onset of excessive sleepiness. These episodes of cataplexy can vary from being very subtle in nature (ie drooping of the eyelids) to complete loss of all muscle groups and collapse onto the floor. There have been some identified associations which have been thought to trigger attacks of cataplexy, such as emotional changes (anger, excitement, happiness and fear).
Sleep paralysis and hallucinations are less commonly experienced. Only 10 to 25 percent of patients who suffer from narcolepsy have all four major symptoms. Episodes of sleep paralysis may occur when patients are falling asleep or waking up. This can be very frightening for the patient as they feel paralysed and trapped, unable to move. They may feel like they are dying or like they are going to remain permanently paralysed and are unable to do anything about the situation. However, these episodes come to an end and patients are left without any permanent effects.
If you have narcolepsy, you may also experience hallucinations. These disturbances are most often visual, but any of the senses can be involved. Hallucinations can be quite disturbing and frightening if you are involved.

How is Narcolepsy Diagnosed?

If you are thought to have narcolepsy, the doctor will usually take a thorough history and perform a physical examination to help support the diagnosis, and to help rule out other causes of sleepiness. A number of tests can also be conducted to help diagnose narcolepsy and rule out other diseases, leaving narcolepsy as an alternative.
Tests to rule out other disorders include:

• Sleep studies
• MRI scan of the brain to exclude masses or brain tumours.
• An EEG (scan of brain activity) to help rule of epilepsy.

Looking at sleep studies, diagnostic testing for narcolepsy involves an overnight polysomnogram. This is followed by a Multiple Sleep Latency Test.
The polysomnogram is a test which evaluates the quality of your sleep. In patients with narcolepsy, there are often spontaneous awakenings and entering REM sleep within the first 20 minutes of the onset of sleep. This test can also identify other causes of sleepiness such as obstructive sleep apnoea.
A Multiple Sleep Latency Test (MSLT) is usually performed the day after the polysomnogram. During the MSLT, you are given multiple opportunities to nap every two hours. Unaffected subjects fall asleep in about 10 to 15 minutes, whereas people with narcolepsy often fall asleep in less than five minutes. If you have narcolepsy, your naps often consist of REM sleep. The onset of these REM periods during your naps is more suggestive of narcolepsy. However, the MSLT has several limitations, which your doctor has to take into account.

Prognosis of Narcolepsy

Narcolepsy commonly appears between the ages of 15 – 30, but regardless of the age of onset, many patients report symptoms worsening over the next few years after the first symptoms appear, before getting better later in life.
In cases where narcolepsy develops in younger children, symptoms are often more severe. These cases are further complicated by some behavioural disorders such as attention-deficit hyperactivity disorder. If this is the case, narcolepsy must be addressed and appropriately managed before the behavioural problem can be tackled. If not treated appropriately, narcolepsy can lead to psychological, cognitive and social problems for children. They may struggle to perform at school, leading to further problems later in life.
Narcolepsy can also have effects on all aspects of daily life such as work, relationships and your health. You may be restricted in the types of jobs you can safely perform, and feel continually drained and exhausted. This can lead to increased accidents and relationship issues. However, there are many strategies to help manage and treat narcolepsy, allowing the patient to lead a productive and safer life.

How is Narcolepsy Treated?

Most patients who suffer from narcolepsy will experience disturbances in their everyday lives, commonly due to excessive daytime sleepiness and cataplexy. Both pharmacological (related to medications) and non pharmacological approaches are important in addressing and treating narcolepsy.

Non pharmacological therapy

There are various interventions that can help you feel better if you experience narcolepsy, that do not involve any medications. These include:

• Sleep hygiene – This refers to timing naps during the day, to improve concentration and sleepiness for the next couple of hours. However, this may be difficult to achieve during weekdays, and also depends on your work / daily routine. Note that symptoms may be worsened if naps are not timed properly. You should sit down with your doctor to try and work out a regular and feasible sleep routine.
• Social support – This is very important in all sorts of conditions, but particularly if you suffer from narcolepsy. You may experience various problems at work, within relationships and the family. Having someone you can talk to about your concerns may help ease the situation and allow you to find a way around these problems. There are common misconceptions which may occur in patients who suffer from narcolepsy. These include: the sleep attacks and excessive daytime sleepiness being due to inadequate sleep during the night, or due to poor motivation. Being in contact with other people who suffer from narcolepsy may help you understand more about the condition and allow you to identify positive coping mechanisms.
• The avoidance of certain drugs which are known to cause sleepiness and drowsiness are also beneficial. Some prescribed and over the counter drugs will make you even more sleepier than usual – if we avoid these drugs, you may begin to feel better.

Pharmacological (Medical) Therapy

Although the above measures may help produce some improvement in symptoms and everyday life, most patients find some benefit from medications that help promote increased alertness and awareness. There are various medications, which can help to maintain increased alertness during certain hours of the day.
Modafinil (also known as Modagavil)
This medication is well tolerated and is one of the first line agents for patients who suffer from narcolepsy. It has been shown to provide good control of sleepiness, promoting wakefulness. The medication is thought to increase levels of chemical substances such as dopamine within the brain and nervous system.
Modafinil is often given once a day, in the morning. There are a few uncommon side effects that may be experienced from this medication, including: dry mouth, decreased appetite. headache, nausea and diarrhoea. It may also cause an increase in blood pressure and is rarely associated with altered heart rhythms. However, under appropriate supervision and medical attention, this medication is usually safe and well tolerated.
There has been a study of about 283 patients with narcolepsy, who were randomised to receiving a dose of Modafinil or a dose of placebo (an inactive substance that is used as a control in an experiment to determine the effectiveness of a medication or other active subject). After nine weeks of treatment, patients who were on the Modafinil demonstrated a significant improvement in sleepiness, as assessed by the Epworth Sleepiness Scale and tests of wakefulness.
Methylphenidate (Concerta)
This medication stimulates the central nervous system to produce increased wakefulness and alertness in the patient. It is effective, in conditions such as attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and narcolepsy. The medication affects chemicals in the nervous system that contribute to hyperactivity and impulse control.
Common side effects include nausea, vomiting, dizziness, nervous problems, changes in sleep patterns and a skin rash. An increase in blood pressure or a fast, pounding heartbeat may also occur. If you have any pre-existing heart problems, it is best that you avoid the use of methylphenidate – rare cases of sudden death have been reported to occur in patients with pre-existing heart problems. However, under appropriate medical supervision and monitoring, methylphenidate can be an effective and useful medication in controlling symptoms of narcolepsy.
Amphetamines (e.g. dextroamphetamine, methamphetamine)
This group of medications also stimulates the central nervous system to improve alertness. Amphetamine medications are usually administered two times a day.
Their side effect profile relates to over stimulation of the central nervous system. These include: effects on the heart and blood pressure, disturbances in mental state, dry mouth, difficulties sleeping and dependence.
Regardless of the choice of medication you are started on, it is very important to make sure you see the doctor on a regular basis, to monitor dosing and address any side effects that occur.

Narcolepsy References

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