What is cataplexy

Cataplexy is a sudden and uncontrollable muscle weakness or paralysis that comes on during the day and is often triggered by a strong emotion, such as excitement or laughter. Without much warning, the person loses muscle tone and can have a slack jaw, broken speech, buckled knees or total weakness in their face, arms, legs, and trunk. A person experiencing total cataplexy stays awake and is aware of what is happening, but cannot move. These episodes last up to a minute or two, and some people may fall asleep afterwards. The frequency of cataplexy episodes varies widely among people with narcolepsy. Some individuals avoid emotions that may bring on cataplexy.

The loss of muscle tone in cataplexy occurs because of the inability to regulate sleep and awake states — meaning that elements of each can overlap. During normal rapid eye movement (REM) sleep, there is a natural loss of muscle tone. In the case of cataplexy, that characteristic of REM sleep occurs suddenly during the day, causing weakness or full paralysis, even as the person remains awake during the episode.

The severity of cataplexy symptoms varies. Some people with narcolepsy never experience an episode of cataplexy, while others have multiple episodes per day. Where you fall in that spectrum, as well as other health considerations, will determine whether your doctor suggests a medication for cataplexy. Some of these medications also have the added benefit of helping with hallucinations and sleep paralysis.

Cataplexy causes

Narcolepsy is a sleep disorder of rapid onset rapid eye movement (REM) sleep that is characterized by excessive sleepiness, daily uncontrollable sleep attacks, sleep paralysis, hypnagogic hallucinations and, for some, sudden loss of muscle control (cataplexy). There are two types: narcolepsy type 1 (formerly narcolepsy with cataplexy) and narcolepsy type 2 (formerly narcolepsy without cataplexy). Narcolepsy is often accompanied by cataplexy (narcolepsy type 1), a sudden loss of muscle control that can cause a person to collapse, slump over, or slur words without much warning. Narcolepsy usually has its onset in childhood or adolescence. Since narcolepsy has an underlying genetic component, family members of people with narcolepsy are at a slightly increased risk of developing the disorder. However, developing narcolepsy is a complex process of genes and triggering events; therefore, many family members of a person with narcolepsy may not have it. Narcolepsy without cataplexy (narcolepsy type 2) includes most of the same symptoms, but its cause is unknown. Injuries to the hypothalamus and brain stem, tumors, and stroke are under investigation.

Prevalence is 25 to 50 per 100,000 people for narcolepsy type 1 (narcolepsy with cataplexy) and 20 to 34 per 100,000 people for narcolepsy type 2 (narcolepsy without cataplexy). Age of onset peaks at 15 and again at 35 years with a 1.6:1 male predominance ¹. Narcolepsy with cataplexy (narcolepsy type 1) has a known cause, related to a loss of cells in the hypothalamus of the brain that secrete the chemical hypocretin (also called orexin) ². The reason for this is not fully understood, but it is thought to be an autoimmune process possibly triggered by an infection ¹. Hypocretin is a chemical in the brain that is important for regulating wakefulness and rapid eye movement (REM) sleep. Normally, alerting signals come from the brain stem, a region deep in the brain responsible for many basic functions. These signals spread out and “wake up” the rest of the brain. Hypocretin activates and maintains the action of those alerting signals coming from the brain stem.

In a person with narcolepsy, the cells in this specialized region of the hypothalamus have died off. Even though it’s a relatively small cluster of cells, the impact on waking and sleep is dramatic. Without hypocretin, it’s hard for a person to stay awake for long periods of time, and they experience overlaps between waking and sleep—such as vivid hallucinations and paralysis when falling asleep or waking up.

The loss of hypocretin also affects the action of other key chemicals in the brain, such as dopamine, serotonin, and norepinephrine. This is why antidepressants (which act on these neurotransmitters) are sometimes prescribed for narcolepsy.

The current understanding of narcolepsy is that it begins with an underlying genetic predisposition; a person is born with certain genes that put them at greater risk for developing narcolepsy. HLA haplotype DQB1*0602 is present in 95% of narcolepsy type 1 patients, but this is also present in about 20% of the general population without narcolepsy ¹. In childhood or the teen years, an event like an 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.

The cause of narcolepsy type 2 is not entirely clear. Current hypotheses include less destruction of hypocretin cells, impaired hypocretin receptor signaling, or an unknown mechanism. Some patients initially diagnosed with narcolepsy type 2 will develop cataplexy indicating disease progression ¹.

The loss of hypocretin in the brain makes it hard for a person to stay awake. It also allows REM sleep to occur in moments when it normally does not. A person with narcolepsy can enter REM sleep directly from a waking state, rather than going through the normal progression from awake, through deep sleep, and eventually into REM sleep.

With narcolepsy, the boundaries between sleep and wakefulness are blurred, causing a person to feel very sleepy and fatigued during the day, have vivid dream-like hallucinations and paralysis while falling asleep or waking up, and experience disrupted nighttime sleep.

While there’s currently no cure for narcolepsy, there are treatments and lifestyle changes that greatly improve the symptoms.

Scientists are working on ways to target and stimulate hypocretin receptors, as a way to mimic the presence of the chemical. They are also working on understanding how hypocretin cells are lost in the first place (the autoimmune response) so they can target the first stage of the process and halt the development of narcolepsy symptoms.

Cataplexy symptoms

Most people who have narcolepsy also experience cataplexy.  Cataplexy is a sudden, temporary bilateral muscle weakness or loss of muscular control lasting a few seconds to a couple of minutes in response to increased emotion (typically laughter) during which patients remain conscious ¹. Cataplexy can also be brought on by excitement, anger, grief, or any strong emotional feeling. Cataplexy is pathognomonic for narcolepsy type 1 if it is present but is not required for the diagnosis of narcolepsy type 2.

Typical cataplexy symptoms are:

• the jaw dropping
• the head slumping down
• legs collapsing uncontrollably
• slurred speech
• double vision or finding it difficult to focus

Some people with narcolepsy have cataplexy attacks once or twice a year, while others experience them several times a day. In an attempt to avoid attacks, some people may become emotionally withdrawn and socially isolated.

Cataplexy diagnosis

The first step in the diagnosis is ensuring that you are regularly getting at least 6 hours of sleep per night for at least 2 weeks. Although this can be done with a patient-reported sleep log alone and still be considered valid for additional testing, patients often overestimate their total sleep time. Two weeks of actigraphy with a sleep log before additional testing is recommended. If the patient is getting less than 6 hours of sleep per night averaged over 2 weeks, they cannot be diagnosed with narcolepsy ³.

If the patient is getting a minimum of 6 hours of sleep per night, then a reasonable next step is a polysomnogram to rule out other possible sleep disorders such as sleep apnea. Following the polysomnogram a Multiple Sleep Latency Test (MSLT) is conducted during the day as long as there were at least 6 hours of sleep during the polysomnogram and no other sleep disorders are found. The patient is given four to five 20-minute nap opportunities at 2-hour intervals. A positive test will show rapid onset of REM sleep (less than 15 minutes) at least twice during the test, and a shortened mean sleep latency averaged across all trials (less than 8 minutes). One of the sleep onset REM periods (SOREMPs) can occur during the polysomnogram with only one during the Multiple Sleep Latency Test (MSLT) and still meet diagnostic criteria. If the Multiple Sleep Latency Test (MSLT) is negative, but there is strong clinical suspicion for narcolepsy, the test should be repeated.

When conducting the Multiple Sleep Latency Test (MSLT), it is important that the patient is allowed to sleep until they wake up on their own from the polysomnogram the night before the test to prevent a possible false positive. If the patient doesn’t get enough sleep the night before the test or it is started too early in the morning, sleep onset REM periods (SOREMPs) may be present of the first couple of naps even in a patient without narcolepsy. Those with chronic insufficient sleep can also have sleep onset REM periods (SOREMPs) on Multiple Sleep Latency Test (MSLT) if they are not screened appropriately with actigraphy and sleep logs before testing.

Narcolepsy type 1 can also be diagnosed if hypocretin-1 is low in the cerebrospinal fluid. Although HLA DQB1*0602 is present in most narcolepsy type 1 patients, there is no common diagnostic utility in testing for it.

Polysomnography

Polysomnography is an investigation of your sleep carried out at a specialist sleep centre. The study usually involves staying overnight at the sleep centre so your sleeping patterns can be analyzed.

During the night, several different parts of your body will be carefully monitored using electrodes and bands that are placed on the surface of your body while you sleep. Sensors will also be placed on your legs and an oxygen sensor is attached to your finger.

A number of different tests will be carried out during polysomnography, including:

• electroencephalography (EEG) – which monitors brain waves
• electrooculography – which monitors eye movements
• electromyography (EMG) – which monitors muscle tone
• recordings of movements in your chest and abdomen
• recordings of airflow through your mouth and nose
• pulse oximetry – which measures your heart rate and blood oxygen levels
• electrocardiography (ECG) – which monitors your heart

Sound recording and video equipment may also be used to record sound and images.

After you have slept, a specialist will analyze your test results to determine whether you have normal brain wave activity, breathing patterns, and muscle and eye movement.

Multiple sleep latency test

A multiple sleep latency test measures how long it takes for you to fall asleep during the day. You may have this test after polysomnography.

You will be asked to take several naps throughout the day, and a specialist will analyse how quickly and easily you fall asleep.

If you have narcolepsy, you will usually fall asleep easily and enter rapid eye movement (REM) sleep very quickly.

You may also have a blood test to find out whether you have a genetic marker known as HLA DQB *0602, which is associated with narcolepsy. A positive result supports a diagnosis, but doesn’t make it 100% certain – 30% of people without narcolepsy also have the genetic marker.

Measuring hypocretin (orexin) levels

Many cases of narcolepsy are linked to a deficiency in the sleep-regulating brain chemical hypocretin, also known as orexin.

Recent research has shown that measuring the level of hypocretin in your cerebrospinal fluid, which surrounds the brain and spinal cord, can be useful in diagnosing narcolepsy.

To measure your level of hypocretin, a sample of cerebrospinal fluid is removed using a needle during a procedure called a lumbar puncture.

This test is increasingly being used by sleep disorder specialists to help make a diagnosis.

This testing could be helpful to confirm or exclude the diagnosis in uncertain cases but is no longer available as of January 2017 ¹.

Cataplexy treatment

First-line treatment for cataplexy is sodium oxybate, is a form of gamma-hydroxybutyrate (GHB) ¹. Sodium oxybate is a liquid solution that is taken at night while in bed due to the short onset of sleepiness, usually 5 to 15 minutes. A second dose is given 2.5 to 4 hours later. Sodium oxybate is the salt form of a chemical that naturally occurs in the brain. It’s a sleep-inducing agent and may help with narcolepsy symptoms by affecting the release of dopamine and noradrenaline—two chemicals that control the sleep-wake balance. It can improve nighttime sleep as well as reduce daytime sleepiness and cataplexy.

Xyrem (sodium oxybate) is a restricted medication being distributed from a central pharmacy ¹. While there are concerns about abuse, dependence and illegal use of Xyrem (sodium oxybate) post-market research has not proven these concerns to be valid.

Antidepressants are commonly used to improve cataplexy. Tricyclic antidepressants (protriptyline, clomipramine) and SNRI/SSRIs (venlafaxine, fluoxetine) have also been used with some success in treating cataplexy ⁴. This is thought to be because antidepressants suppress rapid eye movement (REM) sleep, and the paralysis of REM during waking hours is what causes cataplexy.

References

1. Slowik JM, Yow AG. Narcolepsy. [Updated 2019 Jan 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459236
2. Scammell TE. Narcolepsy. N. Engl. J. Med. 2015 Dec 31;373(27):2654-62.
3. Chang ET, Huang CY, Lai HL. Differences Between Sleep Logs and Actigraphy Combined With Electroencephalography in Adults With Sleep Disturbances. Biol Res Nurs. 2018 Jan;20(1):77-83.
4. Barateau L, Lopez R, Dauvilliers Y. Treatment Options for Narcolepsy. CNS Drugs. 2016 May;30(5):369-79.