What is Kleine-Levin Syndrome (KLS)?
Kleine–Levin syndrome (KLS), also known as “Sleeping Beauty syndrome,” is a very uncommon but severe sleep disorder that includes recurrent episodes of excessive sleepiness. It’s usually accompanied by unusual thinking or behaviors, an uncontrollable urge to eat, and increased sexual drive. The syndrome’s first apparent case was recorded in 1862 by Brierre de Boismont. The syndrome got its name from two physicians – Willi Kleine, who noticed several instances of recurring excessive sleepiness in 1925, and Max Levin, who recorded a case of the same coupled with compulsive eating in 1930.
Critchley and Hoffman further described the syndrome in 1942 and named it after the two initial doctors following their study, “The Syndrome of Periodic Sleepiness and Extreme Hunger (Kleine–Levin syndrome).” Typically, this syndrome affects teenage boys; usually, their episodes may last several weeks before they fully recover. However, these episodes can reoccur multiple times. An episode can last anywhere from a week to one to two months. The duration of KLS can differ based on how the symptoms of the syndrome show up in a patient.
What Causes Kleine-Levin Syndrome (KLS)?
The exact cause of a rare sleep disorder known as Kleine-Levin syndrome has not been pinpointed yet. Some possibilities include emotional distress, injury, exposure to harmful substances, infections, abnormal levels of chemicals in the brain that transmit signals (serotonin or dopamine), and autoimmunity (where the body’s immune system mistakenly attacks normal cells).
It has been suggested that a problem in the hypothalamus (a part of the brain responsible for controlling sleep, hunger, and sexual behavior) could be behind Kleine-Levin syndrome. However, a clear connection has not been established yet.
Research has found a link between increased presence of a specific human leukocyte antigen (a protein that plays a central role in the immune system) known as DQB1 * 0201, and Kleine-Levin syndrome. Theories that the origin of Kleine-Levin syndrome is related to psychological aspects were considered in the 1970s. However, these were mostly dismissed in favor of more concrete, physical causes. Nevertheless, such theories could still be helpful in understanding behavioral issues related to excessive sleepiness seen in Kleine-Levin syndrome.
Some infectious agents such as Epstein-Barr virus, varicella-zoster virus, Asian flu virus, enterovirus, typhoid vaccine, and Streptococcus bacteria, could potentially trigger Kleine-Levin syndrome by causing viral infections. There has been a noteworthy correlation between an upper respiratory infection (like a common cold) and a symptomatic episode of Kleine-Levin syndrome.
Risk Factors and Frequency for Kleine-Levin Syndrome (KLS)
Kleine–Levin syndrome is an extremely rare condition. A systematic review from 1962 to 2004 found only 186 known cases worldwide. It is estimated that there are between 1 to 5 cases per million people. The majority of these cases are in Western countries, but around one-sixth of the patients were found in Israel. Men are twice as likely to be affected than women, and the syndrome mainly affects teenage boys with the median age of onset at 15 years. About 81% of all cases are noted to start during a person’s second decade of life. It’s uncommon for people older than 30 to experience their first bout with Kleine–Levin syndrome.
- Triggers for the onset of Kleine–Levin syndrome could include:
- Infections, such as cold or fever
- Alcohol use
- Sleep deprivation
- Head trauma
- Physical exertion
- Unusual stress
- Traveling
- Marijuana use
Signs and Symptoms of Kleine-Levin Syndrome (KLS)
Kleine-Levin syndrome is a disorder characterized by extreme sleepiness and other unusual behaviors. People with the condition have bouts of excessive sleepiness, often sleeping 12 to 24 hours a day. Before these episodes, they might feel incredibly tired. If their sleep is disturbed, they can become irritable or aggressive but may not remember their actions afterwards. Interestingly, they can be awakened and may even get up to eat or use the bathroom.
In early episodes, the need for sleep is particularly noticeable, while later episodes seem to be dominated by extreme fatigue. Many people with Kleine-Levin syndrome also have issues with thinking clearly, paying attention, and memory. They may speak oddly, experiencing problems like not talking at all or slurring their speech. They may also forget things, lose track of time, and have strange perceptions of the world.
In addition to sleep disturbances, Kleine-Levin syndrome can also cause changes in appetite and mood. Around 75% of
people with the disorder overeat and crave sweets during their episodes. This could lead to consuming six to eight meals a day and gaining between 7 and 30 pounds. About half of the people with this condition feel depressed during their episodes, and women are more vulnerable to this than men. Suicidal thoughts occur in about 15% of cases. Around 50% of people with the syndrome display signs of increased sexual urges during their episodes, which is more common in men.
Other behaviors may be driven by compulsion, such as repeated singing, rocking back and forth, lip chewing, and inappropriate writing on walls. They
may also have a sense of being detached from reality, as though they were in a dream or disconnected from their surroundings. Some of them may even experience visual or auditory hallucinations and become paranoid.
Testing for Kleine-Levin Syndrome (KLS)
Diagnosing Kleine-Levin syndrome can be tricky. This condition can only be identified by ruling out other diseases that have similar symptoms. Diagnosing Kleine-Levin syndrome usually involves observing the main symptoms: excessive sleep (hypersomnolence), overeating (hyperphagia), and increased sexual drive (hypersexuality). These symptoms must be noticed along with the assurance that the cause is not metabolic, neurological, or psychiatric.
CT and MRI scans of the brain generally appear normal, meaning that the brain’s shape and structure don’t show any obvious signs of disease. An EEG, a test that measures the electric activity in the brain, often reveals slower than normal rhythms. A sleep study (polysomnography) typically shows an increase in total sleep duration.
Some peculiarities in the sleep pattern have been recorded in people with Kleine-Levin syndrome. For example, during the early stages of an episode, ‘slow-wave sleep’ (the deepest phase of sleep) can be reduced, even though symptoms continue, it eventually returns to normal. On the other hand, ‘rapid eye movement’, or REM sleep (the phase of sleep where we dream), might be normal early in an episode, but decrease as the episode progresses.
The Wechsler Memory Scale, a test used to measure memory performance, is often used to assess the working memory in patients with Kleine-Levin syndrome. Usually, patients with this syndrome have a lower than average score on this test.
Treatment Options for Kleine-Levin Syndrome (KLS)
Kleine-Levin syndrome is a complex condition, and, unfortunately, there is no definitive cure for episodes or the period in between them. That being said, a few approaches can help manage the condition. Non-drug treatments for Kleine–Levin syndrome can consist of psychological education and ongoing support.
Although no one medication has proven wholly effective, several have been trialed. These include psychotropic drugs, a class of medication that changes brain function, like lithium, anticonvulsants, which are used to treat seizures, and antidepressants, primarily used to treat depression.
Antidepressants have generally not prevented the condition from recurring, except for one case where a specific antidepressant – a monoamine oxidase inhibitor called moclobemide – was used. The medication Carbamazepine has shown some success in improving unusual behavior. Similarly, Lithium has significantly helped by reducing episode duration, preventing relapses, and enhancing recovery from symptoms.
Risperidone, a type of medication called an antipsychotic, may help with severe symptoms and help rebalance sleep cycles. Meanwhile, drugs called dopamine agonists and gabapentin could also be effective.
Modafinil, a medication used for sleep disorders, has shown promise by shortening the times when symptoms are present, but it didn’t impact the recurrence rate. Several stimulants, including methylphenidate, ephedrine, methamphetamine, and amphetamine, can help with sleepiness, but they don’t seem to affect cognitive or mental impairment.
What else can Kleine-Levin Syndrome (KLS) be?
Kleine–Levin syndrome is a condition that can often be confused with mental health disorders. It’s possible to mistake it for a range of other conditions, such as:
- Atypical depression
- Severe depression
- Bipolar disorder
- Narcolepsy
- Klüver-Bucy syndrome
- Menstruation-related hypersomnia
- Brain lesions
- Mitochondrial disease
- Urea cycle defects
- Lyme disease
- Acute intermittent porphyria
- Temporal lobe epilepsy
It’s even more challenging to diagnose Kleine–Levin syndrome when symptoms of major depression, bipolar disorder, and suicidal thoughts are pronounced. They can often overshadow the signs of Kleine–Levin syndrome and delay accurate diagnosis.
What to expect with Kleine-Levin Syndrome (KLS)
Kleine-Levin syndrome usually has a good outcome and is typically followed by a natural disappearance of symptoms. On average, patients tend to have a break of about 6 months between bouts of the illness, and these episodes gradually lessen in their frequency and severity over time. Patients are believed to be recovered if they don’t have any more episodes for at least six years.
When it comes to how long the condition lasts, it normally tends to be around 10 years in patients with Kleine-Levin syndrome who don’t experience hypersexuality. But for those who do experience this symptom, the disease generally lasts for about 21 years.
Possible Complications When Diagnosed with Kleine-Levin Syndrome (KLS)
Kleine-Levin syndrome, when left untreated, does not result in any known long-lasting complications. This condition naturally gets better on its own over time.
Preventing Kleine-Levin Syndrome (KLS)
If you’re experiencing unusual sleeping patterns, for example those observed in Kleine-Levin syndrome, it’s essential to discuss this with your doctor who may recommend further evaluation by a sleep specialist. Kleine–Levin syndrome is a rare sleep disorder characterized by persistent episodes of excessive sleepiness and cognitive disturbances. Here are how different healthcare professionals may be involved in your care:
Your doctor will help you understand what to expect throughout the disease progression and advise about potential symptoms you may experience. Nurses may offer additional advice and check how well treatments are working. Pharmacists are there to ensure that your medication is given in the correct dosage and without interactions with other drugs. They can also educate you about how to take your medication and potential side effects.
You should also know that Kleine-Levin Syndrome is generally a benign condition, meaning it will not cause any lasting harm or long-term complications. To help you manage this condition and achieve the best possible results, all your healthcare professionals will work together as a team.
