Forgotten Diseases Research Foundation

Kleine-Levin Syndrome (KLS)

Kleine-Levin Syndrome (KLS) is a chronic sleep disorder and is one of the central disorders of hypersomnolence (CDHs). This term refers to conditions that cause excessive daytime sleepiness, meaning that patients have trouble staying awake during the day (1). CDH-type sleepiness isn't caused by temporary loss of sleep or by misaligned circadian rhythms (a preferred sleeping schedule that's shifted from times that are typical of the rest of the population --- jet lag is an example). Rather, the problem in the CDHs is internal, and it happens over an extended period of time (generally, for at least three months).

Some people with CDHs may feel increasingly drowsy as the day goes along, and need to take a nap. They may or may not feel refreshed when they wake up, and they may feel drowsy again later. Others may have sleep attacks, which cause them to fall asleep suddenly, without feeling drowsy first. Others may become sleepy when doing something that isn't mentally stimulating, such as sitting in the passenger seat of a car. Some may be able to put naps off by doing something active. Many sleep for at least hours per night, yet are still tired during the day.

Daytime sleepiness can be assessed with an easy-to-use quiz called the Epworth Sleepiness Scale (2). The quiz has 8 simple questions and a basic scoring system. Higher scores (10 or more points) indicate the possibility of excessive sleepiness and suggest that seeing a doctor may be a good idea; scores of 16 or more are strongly suggestive of excessive daytime sleepiness and the need to see a doctor. In addition to this scale, physicians can study sleep with specialized tests, such as an MSLT (Multiple Sleep Latency Test) and polysomnography. The MSLT measures sleep latency, which is how quickly a person falls asleep. Polysomnography measures a variety of physiological states while a person is sleeping. Both are used for studying sleep and for diagnosing sleep disorders.

Other central disorders of hypersomnolence include idiopathic hypersomnia, narcolepsy, insufficient sleep syndrome, and hypersomnia due to medical/psychiatric disorders or to medications or other substances. Overall these conditions are rare to very rare, with narcolepsy being the most common.

Clinical information

KLS is a disorder that causes people to sleep excessively (hypersomnia). A standout feature of KLS is that sleepiness occurs in episodes that last for days, weeks, or even months. In between episodes, patients typically have normal sleep patterns, after which excessive sleepiness then returns. During an episode, patients sleep for an average of 18 hours a day (up to 24 hours a day in some cases; 3).

KLS tends to affect young people, with adolescent males being most commonly affected (3, 4). Attacks may occur several times per year, but with time, the intervals between them may get longer and the attacks may become less severe. In most patients, the condition eventually seems to go away after several years or more. The reasons for this are not known.

KLS is a very rare disease; a recent study estimated its prevalence at 1.8 cases per million people in France (5). However, it may be more common among people of Ashkenazi Jewish origin (6). Like many rare disorders, KLS is probably underdiagnosed.

KLS has been reported in people of a variety of ethnicities and locations. It has been reported in many countries in Europe (6), in India (7), the Middle East (8), South Africa (9), South America (10, 11), North America (6), and eastern Asia (12-14). This list is not comprehensive.

KLS is characterized by sudden-onset episodes of hypersomnia, which may be preceded by a fever, use of alcohol, and other factors (see Cause and Triggering Events below for more information). During a sleepiness episode, a person may only awaken to eat and use the toilet. Some patients may be easy to awaken, though doing may also cause them to be irritable or even aggressive. Many patients report feeling apathetic about their surroundings or disconnected from reality during a sleep episode.

KLS is also characterized by other problems that do not occur when the patient's sleep/wake rhythm is normal. For example, excessive eating is a common feature of KLS, and may occur even though the patient does not feel hungry. Patients will often eat anything that is put in front of them or any food that they happen to see. An example is of a young man who ate dinner and then saw a plate of sausages and tomatoes. He ate them all, and then ate half a loaf of bread (15). This man noted that he would "go on eating until there was no more."

Memory loss during a sleep episode is also common in KLS, and some patients may become sexually uninhibited. The latter problem is more common in males than females, and it tends to create feelings of embarassment or shame afterwards in people who remember them.

Signs and symptoms

The most common clinical features of KLS are listed below. These features are common during sleep episodes, and are typically not present between them.

    Common problems in KLS

  • Hypersomnia that relapses and remits
  • Cognitive impairment
  • Altered perception of reality
  • Confusion about time or place
  • Trouble making a decision
  • Difficulty concentrating
  • Reading difficulty
  • Memory loss
  • Apathy
  • Speech abnormalities
  • Behavior changes
  • Sexual disinhibition (more common in males)
  • Intense dreams that seem real
  • Excessive eating
  • Depression
  • Insomnia after an episode ends

Although excessive eating or an increased appetite are more common, a minority of patients feel decreased appetite during sleep episodes.

Cause and Triggering Events

The cause of KLS is currently unknown. As noted above, it appears to be triggered by various events in a majority cases (3). The most common trigger is a fever or a minor flu-like illness; in these cases, sleepiness appears to occur within 3-5 days (3). Alcohol consumption has also been noted in a number of cases. In one case, the patient drank excessively and exercised vigorously before two episodes (15). Less common triggering events include marijuana use, stress, surgery with anesthesia, jet lag, and migraine (reviewed in 3).

KLS may also be associated with menstruation in females. In the past, this problem was considered to be a separate condition from KLS, but it has now been classified as a form of KLS (16).

KLS has been reported in a small number of families (reviewed in 17) and in two sets of identical twins (18, 19). These findings imply that there is some kind of genetic component to KLS in addition to physiological factors brought on by triggering events. However, at this time, there are no gene mutations associated with risk for KLS.

Diagnosis and Testing

KLS is usually suspected because of episodic sleep abnormalities accompanied by behavior changes. Unfortunately, there are no laboratory tests for it. This means that diagnosis is based on clinical observation and on tests that exclude other conditions (see Differential Diagnosis, below). In addition, diagnostic criteria have been established for KLS and refined periodically. The list below lists the most current diagnostic criteria (16):

  • Repeated episodes of excessive sleep that last from 2 days to several weeks;
  • Episodes usually occur at least once per year but at least once every 18 months;
  • In between sleep episodes, the patient's alertness, cognitive function, behavior, and mood are normal;
  • At least one of the following occurs during sleep episodes: cognitive problems, altered perception (usually a feeling of derealization, or a feeling that the person's surroundings are not real), an eating disoder (usually excessive eating, but poor appetite is also possible), or loss of inhibitions (e.g. sexual inhibitions);
  • The symptoms are not better explained by drugs, medications or another disorder (e.g. depression, bipolar disorder, neurologic, metabolic, or mental disorders).

As may be inferred from the table, laboratory and clinical tests are of little help in diagnosing KLS. EEGs may be abnormal, showing nonspecific diffuse background slowing; however, a quarter of patients have normal EEGs during sleep episodes (20). Brain imaging also appears to be generally normal (20). However, an MRI study of 41 patients found hypoperfusion in the thalamus, the hypothalamus and the caudate nucleus in patients who were between sleep episodes (21).

Differential Diagnosis

The differential diagnosis for KLS includes drugs and prescribed medications (e.g. cannabis, illicit drugs, alcohol, benzodiazepines). Urine tests may confirm or exclude use of these agents, although their presence does not necessarily exclude a diagnosis of KLS if use was very recent. This is because some of these agents (e.g. alcohol and cannabis) have appeared to trigger KLS (see Cause and Triggering Events, above). Three other conditions in the differential diagnosis of KLS are described below; for more information on other conditions that are related to KLS, see references 16 and 20.

Encephalitis. Encephalitis means swelling of brain tissue. It can cause flu-like symptoms, including headache and fever, as well as neurological symptoms such as drowsiness, confusion, clumsiness, irritability, and sensitivity to light. All of these problems are associated with KLS. However, encephalitis is often caused by infection with a virus, and testing is possible. Thus, any person with these problems and a fever should be tested for encephalitis. Testing may involves obtaining a sample of blood or spinal fluid, as well as imaging studies and/or an EEG.

Widespread vaccination in recent decades has reduced the incidence of this encephalitis. Vaccine-preventable conditions that can cause it include measles, chickenpox, rubella (German measles), mumps, polio, and rabies.

Narcolepsy is another sleep disorder that makes patients feel very sleepy during the daytime, regardless of the amount of sleep the previous night. Unlike KLS, however, narcolepsy is a consistent problem, and there are no periods of sleep/wake normality in the way that there are with KLS. In addition, and in contrast to KLS, sleep episodes in narcolepsy often last for no more than a few minutes (though they may last for over an hour), and may feel refreshing (though the person may feel drowsy again later). In addition, and unlike KLS patients, narcolepsy patients may experience cataplexy, which is a sudden loss of muscle tone while awake. This problems provokes a feeling of weakness and/or loss of muscle control; patients may collapse or have trouble speaking. Patients are always awake and aware of the problem. It may be very mild (affecting the eyelids only) or very severe (affecting all muscles). For more information on narcolepsy, see reference 22.

Idiopathic hypersomnia IH (or IHS) is a condition in which people sleep excessively. However, unlike people with KLS, idiopathic hypersomnia occurs consistently and is not associated with periods of normal sleep/wake patterns. People with IH usually feel sleepy during the day. They may also sleep a lot at night, and may not wake up feeling refreshed.

There are two types of IH. In the first, the patient doesn't sleep excessively at night (9 hours or less). Patients with the second form sleep longer than usual at night. In both types, there is excessive daytime sleepiness, and patients may take naps that may last up to several hours. The naps are not refreshing. Patients may also have trouble with memory and concentration. Increased appetite and sexual disinhibition do not appear to be features of IH.



References

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Page last modified on 10 March 2017.