Narcolepsy: causes, symptoms, diagnosis and treatment

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and drowsiness. It is basically a neurological disorder that disturbs the brain’s ability to regulate sleep-wake cycle. People with narcolepsy have trouble falling asleep at night while they suffer from irresistible episodes of falling asleep during the daytime. Such sleep attacks are sudden and may occur during any time of the day or during work. If you find a person falling asleep in the middle of talking, eating or any other activity you should suspect that he might be suffering from narcolepsy. Brain controls our sleep in the form of well developed cyclic pattern.

To understand narcolepsy fully, we need to understand the normal regular sleep cycle. There are two main phases of sleep- non rapid eye movement (NREM) and rapid eye movement (REM). In typical sleep, we progress from the initial stages of sleep to deeper sleep stages. The first phase during sleep is non rapid eye movement, after about 90minutes this stage is replaced by the rapid eye movement. One dreams during this REM phase, in this phase, muscles become limp; this immobility prevents one from moving and acting out of dreams. In people with narcolepsy REM sleep occurs immediately, not preceded by a NREM.

Causes of narcolepsy

Genetic abberations

According to the latest research, narcolepsy is strongly associated with genetic abnormalities. Many genes and proteins control our sleep patterns. According to one of the proposed mechanisms, narcolepsy involves an area on chromosome 6 known as human leukocyte antigen (HLA).

Variations in the HLA cause the brain neurons (nerve impulse transmitting cells) to release some proteins. These proteins are known as hypocretin or orexn. It is actually these proteins that control our sleep and appetite patterns. In narcoleptic patients there is reduced production of hypocretin due to decreased number of hypocretin producing neurons leading to irregular sleep patterns. In addition, the brain cells have certain genes that influence narcolepsy in one way or the other. These genes control the production of chemicals involved in the sleep-wake cycle. Any abnormality in these genes can disrupt our regular sleep patterns.

Auto-immune responses

Narcolepsy can also occur as a result of an autoimmune response. Whenever a foreign particle enters into the body antibodies are produced to destroy it. But in some conditions, these antibodies can be formed against body normal cells. Same is the case in narcolepsy in which antibodies are formed against hypocretin secreting normal, healthy cells and attack those areas of the brain that are involved in the production of hypocretin. This leads to its insufficient production of hypocretin, contributing to sleep disturbances.

Normal sleep pattern versus narcolepsy

As already described one goes from non-rapid eye movement (NREM) to rapid eye movement (REM) phase during sleep. In narcolepsy the non rapid eye movement sleep is totally absent. Absence of NREM leaves only rapid eye movement in these patients at both day and night times. REM sleep will lead to transient muscle paralysis, sleep abnormality and excessive vivid dreams in such patients.

Heredity

As narcolepsy is associated with gene mutations, this mutant/ abnormal gene can be transmitted through inheritance. Narcoleptic individuals inherit genes affecting hypocertin. Researches have shown that heredity contributes to 10% of all causes of narcolepsy. So, there is a higher risk of narcolepsy in those people whose relative have narcolepsy.

Infections

Some infections can directly or indirectly cause narcolepsy. It is due to the effect of these infections in the brain, particularly those associated with hypocretin secretion that causes narcolepsy.

Injury or trauma

Brain injury can occur due to stroke, brain tumors and trauma to the brain due to accidents or brain trauma. These brain injuries affect those parts of the brain involved in the rapid eye movement phase of sleep or hypocretin secretions. This causes sleep disturbances, ultimately leading to narcolepsy.

Environmental factors

Environment also plays a role in narcolepsy. The environment contains many harmful toxins. Environmental toxins include smoke, weed killers, pesticides, insecticides and heavy metals. These toxins can exert direct or indirect effects on the brain leading to narcolepsy. Dietary factors, stress and hormonal changes and changes in sleep schedule also contribute to narcolepsy through the same mechanism.

Signs and symptoms

Excessive daytime sleepiness

The first symptom that appears in narcoleptic patients is excessive daytime sleepiness (EDS). EDS interferes with regular daily activities with or without affecting sleep at night. EDS is a sense of mental cloudiness associated with depressed mood, lack of sufficient energy, overwhelming tiredness and fatigue. People find it very difficult to keep themselves awake during work in school, office or home and maintain their concentration. They fall asleep irresistibly and feel refreshed for a few hours on awakening. These episodes of uncontrollable sleep are very brief and are thus called micro-sleeps. These micro-sleeps last from seconds to minutes. During these sleep episodes some people keep on performing their habitual activities such as taking notes, typing, driving with no memory on awakening. The only clue they get is illegible writing or an accident that can occur while driving in sleep.

Cataplexy

Cataplexy is sudden loss of muscle tone leading to a feeling of weakness and loss of voluntary movements. Cataplectic attacks can occur during any time of the day. The duration and severity of the attacks vary from one attack to the other. In mild attacks the loss of tone is slight causing sense of mild weakness in some muscles. Complete loss of muscle tone occurs in most severe attacks leading to collapse- in which people are unable to move their body, unable to speak, and cannot keep their eyes open. The loss of muscle tone that occurs in these patients resembles that of REM, because both events occur from the same group of neurons. Cataplexy is often triggered by intense emotions such as laughter, surprise, anger, fear, stress, humor or excitement.

Sleep paralysis

Sleep paralysis is the temporary inability to move or speak while waking up or falling asleep. The episodes of sleep paralysis are brief, usually lasting from a few seconds to a few minutes. People are fully conscious in these episodes and after episodes end people readily regain their full capability to work and speak.

Hallucinations

Hallucination is an apparent perception of something that is not present in reality. Hallucinations can occur when people are falling asleep, during sleep or waking. Visual hallucination occurs in such patients primarily. Such experiences are vivid and frightening. Hallucinations of the other senses can also occur. Hallucinations that occur during sleep are called as hypnagogic hallucinations while hallucinations that occur while person being awake are known as hypnopompic hallucinations.

Micro naps

It is falling asleep for a few seconds associated with an overwhelming urge to sleep.

Night-time wakefullness

People with narcolepsy suffer night time wakefulness; they have episodes of wakefulness at night with elevated heart rate, hot flashes and intense alertness.

Obesity

Obesity is associated with narcolepsy in some people. These people suddenly gain weight. When narcolepsy is treated obesity also subsides.

Disrupted nocturnal sleep

Some narcoleptic patients have no difficulties in falling asleep at night, but they have extreme problems of staying asleep. These people wake up many times during sleep and feel that their sleep is not soothing enough. Disrupted nocturnal sleep leads to insomnia, periodic leg movements, talking during sleep, vivid dreaming and walking or driving during sleep.

How narcolepsy is diagnosed?

History and examination

A detailed medical history is necessary to diagnose narcolepsy. Narcoleptic patients give a detailed history of excessive daytime sleepiness. A doctor may ask patients to keep a record of their sleep, its duration and symptoms. Clinical examination is also necessary as it helps to rule out other neurological conditions that can disturb sleep.

Epworth sleepiness scale

It is a simple test that helps in measuring the severity of the conditions in narcoleptic patients. In this test a scale is used called as Epworth sleepiness scale, in which people rate the likelihood to fall asleep or sleepiness. A score of 10 or greater indicates sleep disorder.

Nocturnal polysomnogram

Polysomnogram is an overnight test which takes measurements many times while the individual is sleeping. It records respiratory rate, heart rate and movements of muscles and eyes. It also measures electrical and nerve activities in the brain using special devices. This test can also reveal the timing of rapid eye movement sleep. So, by using this test one can detect early rapid eye movement sleep that occurs in these patients.

Multiple sleep latency test (MSLT)

MSLT detects tendency of a person to fall asleep during the day. It measures the duration of time that a person takes in falling asleep. Normally sleep latency period is about 12 minutes or longer. In this test, an individual is instructed to take four of five naps of short duration over the course of a day. These naps are scheduled two hours apart. A latency period of 8minutes or less indicates excessive daytime sleepiness due to narcolepsy. People going directly into REM sleep or just after few minutes are indicative of narcolepsy.

Spinal fluid analysis

It is a new diagnostic test for narcolepsy that is gaining importance. This test measures levels of hypocretin in cerebrospinal fluid. Reduced levels of hypocretin that are detected by this test is a marker for narcolepsy.

HLA typing

Human leukocyte antigen typing can also be helpful in detecting narcolepsy.

Treatment

There is no cure for narcolepsy, but lifestyle changes and medications can help manage the symptoms.

Lifestyle modifications

Lifestyle changes, in combination with support and counseling, can help manage narcolepsy symptoms. Exercise, diet and stress management can also play a great role in maintaining sleep-wake cycle. Regular sleep schedule, relax bedding and peaceful environment can help alleviate the symptoms of disrupted sleep. Some lifestyle modifications are listed briefly as follows:

Regular sleep schedules

Go to bed and wake up at the same time daily including weekends. Night hours should be specified. One should stick to this schedule firmly.

Take naps

Plan brief, regular, short naps during the daytime at regular intervals. Naps of 15-20 minutes are proved to be refreshing and can reduce sleepiness for almost 2-3 hours.

Regular exercise

Do regular walks during the day. Schedule moderate, daily exercises at least 4-5 hours before bedtime. These exercises make one feel more awake and conscious during the day and stimulate better sleep at night.

Warm bath

A warm bath before bedtime makes one relax, which induces better sleep.

Maintain a peaceful atmosphere of the room

Make adequate, suitable bedroom environment. Keep your bedroom quiet, dark, comfortable and free of distractions like TV.

Avoid caffeine, tobacco, nicotine, alcohol, chocolate

Avoid these stimulants, especially at night as these substances make one more active and conscious. Also do not drink too much coffee while on medication, such as Zoloft.

Avoid drugs that can cause drowsiness

Some drugs like anti-allergy drugs and cold medications can make one drowsy. These drugs should be avoided, especially during the daytime.

Take healthy diet

Take healthy diet rich in vegetables, fruits, whole grains and meat. Healthy diet induces healthy sleep.

Relax and manage emotions

Relaxation techniques like yoga, breathing exercises or massage can help manage intense emotions that can trigger narcolepsy.

Avoid activities that would be harmful

Dangerous activities like driving when one is drowsy should be avoided. If necessary, these activities should be started after taking a nap.

Carry a tape recorder

As there is a chance of falling asleep in the office, school, or during work, one should carry a tape recorder to record important meeting and lectures.

Avoid large meals before bedtime

Large, heavy meals before bedtime should be avoided as these can increase metabolism which hinders peaceful sleep.

Medications

Stimulants

Drugs that stimulate central nervous system are the mainstay of primary treatment for narcolepsy. These drugs include modafinil (provigil) and armodafinil. They are stimulants and help in maintaining daytime alertness and wakefulness without causing addiction. Methylphenidate and other amphetamines can be used, but these drugs cause greater side effects and addiction.

Tricyclic antidepressants

Tricyclic antidepressants include clomipramine and imipramine. They suppress some symptoms of narcolepsy like cataplexy.

Xyrem

Xyrem, also known as sodium oxybate, is very effective in managing cataplexy. Xyrem promotes deep and sound sleep, reduces daytime drowsiness and decreases the incidences of cataplexy, but it can cause serious side effects like bedwetting, breathing difficulties, coma and death.

Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs)

These medications suppress REM sleep and help to alleviate some of the symptoms like hypnagogic hallucination, cataplexy and sleep paralysis.