Kleine-Levin Syndrome

What Causes Kleine-Levin Syndrome?

Scientists don’t know what causes KLS. The disorder’s characteristic cluster of symptoms leads researchers to believe that the origin of the condition lies in the hypothalamus, the part of the brain that regulates sleep and appetite. An injury or infection that damages the hypothalamus could trigger the onset of KLS.

The involvement of flu-like symptoms before an episode in many cases has led some scientists to speculate that KLS is an autoimmune disorder. If this is the case, the body’s immune system may respond inappropriately to an infection by attacking healthy cells, possibly in the hypothalamus.

Is Kleine-Levin Syndrome Hereditary?

Because the cause of KLS is unknown, it is difficult to say whether or not genetics play a role in the onset of the disorder. In most cases, there is no family history of KLS, but in rare cases there is, suggesting that there may be an inherited component to the condition. It is also possible that some individuals may have a genetic predisposition to respond to infections in a way that triggers KLS.

How Is Kleine-Levin Syndrome Detected?

KLS usually has a rapid onset and begins with no warning, so there is likely no way to detect it before an episode occurs. Some of the symptoms of KLS are similar to those of mood disorders such as depression; misdiagnosis of those disorders may happen. On average, the time between the onset of KLS symptoms and an accurate diagnosis is about four years.

Because KLS symptoms overlap with those of other serious, potentially life-threatening conditions, people who experience periods of hypersomnia and other KLS symptoms should seek the advice of a doctor.

How Is Kleine-Levin Syndrome Diagnosed?

No test can definitively diagnose KLS. In most cases, a doctor will begin the diagnostic process by ruling out other conditions that can have similar symptoms, such as:

• Diabetes
• Hypothyroidism
• Tumors or lesions
• Multiple sclerosis
• Epilepsy
• Meningitis
• Encephalitis
• Narcolepsy
• Depression
• Bipolar disorder

When other possible diagnoses have been ruled out, a doctor can consider KLS as a possibility. The International Classification of Sleep Disorders manual includes criteria that can support a KLS diagnosis. To meet the criteria, a patient must have had recurrent periods of excessive sleep (hypersomnia) lasting 2-31 days each. In addition, the patient must have had one more associated symptoms, such as:

• Cognitive problems (confusion, hallucinations, disconnection from reality)
• Behavioral problems (irritability, aggression, apathy)
• Excessive eating
• Hypersexuality

Long, symptom-free periods of normal sleep must also occur between episodes.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Kleine-Levin Syndrome Treated?

KLS has no cure, and there is no standard treatment for its symptoms. In most cases, doctors will recommend at-home monitoring of the episodes to prevent complications. In some cases, medications may be used to treat specific symptoms:

• Amphetamines or other stimulants may effectively reduce hypersomnia, but they typically don’t improve other symptoms and may have side effects.
• Mood-stabilizing drugs such as lithium have been shown to shorten episodes in some cases.
• The anticonvulsant drugs carbamazepine and phenytoin have been used in a small number of cases, but research has not yet conclusively proven their effectiveness.

How Does Kleine-Levin Syndrome Progress?

KLS episodes usually become less frequent and less severe over time. In some cases, symptoms disappear permanently by the time the sufferer reaches adulthood. In many other cases, episodes occur periodically well into adulthood.

How Is Kleine-Levin Syndrome Prevented?

Because the cause of KLS is unknown, there is no known way to prevent the disorder. Although some evidence points to a possible genetic connection in some cases, no definite link between any specific gene or genes and the disorder has been identified. Therefore, it is not possible to with certainty that someone with KLS has an increased risk of passing the disorder on to their children.

Kleine-Levin Syndrome Caregiver Tips

KLS typically lasts for years and affects children at an already challenging time in their lives. Parents of children with KLS should keep some key points in my mind to help themselves and their children live with the disorder.

• Know how to take care of your child. In the middle of a KLS episode, your child won’t be able to take care of themselves. Educate yourself about the disorder’s potential complications, so you know how to keep your child healthy and safe.
• Understand how the disorder affects your child, and be an advocate. People who don’t understand KLS may be judgmental about your child’s experience with the disorder. It’s up to you to ensure that your child’s peers, teachers, and others respect your child’s struggle with the condition.
• Get help from the KLS community. The KLS Foundation maintains a collection of resources meant to provide education and support for families and individuals living with KLS.

Some people with KLS also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with KLS:

• Anxiety and depression are common in people with KLS.
• People with KLS may be at increased risk for suicidal behavior.
• Bipolar disorder or eating disorders are sometimes associated with KLS.
• Psychotic disorders resembling schizophrenia have sometimes been linked with KLS.

Kleine-Levin Syndrome Brain Science

The cause of KLS remains elusive, but researchers are conducting studies in several different areas to understand how the disorder happens. Areas of recent research include:

• Functional brain imaging. Researchers have used fMRI imaging scans to examine how the brains of KLS patients function both during and between episodes. In some cases, the subjects show decreased activity in several areas of the brain, including the temporal and frontal lobes, thalamus, and hypothalamus. However, the results so far have been inconclusive.
• Immunology. Some KLS symptoms strongly suggest that the immune system plays a role in the condition. Some scientists think KLS might be an autoimmune disorder. Scientists who support this hypothesis advocate more research into using immunosuppressive therapies to treat KLS.

Kleine-Levin Syndrome Research

Title: Clarithromycin Mechanisms in Hypersomnia Syndromes

Stage: Recruiting

Principal Investigator: Lynn Marie Trotti, MD

Emory Sleep Center

Atlanta, GA

The purpose of this study is to evaluate a medication called clarithromycin for treating sleepiness in two related conditions, narcolepsy without cataplexy and idiopathic hypersomnia. Studies have shown that clarithromycin can reduce sleepiness, but researchers do not know how clarithromycin does this. This study will look at brain activity (on magnetic resonance imaging [MRI] and electroencephalogram [EEG] brainwaves), inflammation, bacteria living in the gut, and cerebrospinal fluid, to better understand how clarithromycin can reduce sleepiness. This study will recruit 92 participants who will be randomized to receive clarithromycin or a placebo for 14 days.

Title: Modafinil Versus Amphetamines for the Treatment of Narcolepsy Type 2 and Idiopathic Hypersomnia

Stage: Recruiting

Principal Investigator:  Lynn Marie Trotti, MD, MSc

Emory Sleep Center

Atlanta, GA

For diseases that cause excessive daytime sleepiness (such as narcolepsy and idiopathic hypersomnia), several medications can be used to treat sleepiness. However, it can be challenging to decide which medication to use for a particular individual for several reasons: 1) there are very few studies that directly compare two medications to see which works best; 2) there are very few studies that include people with a disorder of sleepiness called idiopathic hypersomnia.

To address this knowledge gap, the researchers propose a randomized clinical trial comparing modafinil and amphetamine salts in patients with narcolepsy type 2 or idiopathic hypersomnia. All participants will either receive modafinil or amphetamine salts — no participant will receive a placebo.

This study will evaluate which medication works better to improve sleepiness. The researchers will also see which drug is better for other symptoms, including difficulty waking up and difficulty thinking and seeing which medication causes fewer side. Finally, this study will see if any information about patients (such as age or sleep study features) predicts responding better to one medication or the other.

Title: Rare Disease Patient Registry & Natural History Study – Coordination of Rare Diseases at Sanford (CoRDS)

Stage: Recruiting

Principal Investigator: Benjamin Forred, MBA

Sanford Health

Sioux Falls, SD

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as efficiently as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals, and researchers to assist in advancing research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to register.