What Is Kleine-Levin Syndrome?

Overview

Kleine-Levin syndrome, also known as sleeping beauty syndrome or familial hibernation syndrome, is a rare sleep disorder characterised by episodes of excessive sleepiness where one may sleep up to 20 hours per day, extreme appetite, strong sexual urges, as well as other dysfunctional thinking patterns and behaviour, which last from a couple of days to several weeks at a time. These episodes are typically separated by periods of normality, where patients sometimes forget what occurred in preceding episodes. Whilst Kleine-Levin syndrome can occur in anyone, and its cause is not completely understood, its onset predominates in adolescents assigned to males at birth. Spontaneous recovery is common, gradually occurring with age, though a minority of cases, that is about 15 per cent, show no signs of recovery after a couple of decades with the disorder. There is not a one-size-fits-all treatment for Kleine-Levin syndrome nor a pharmacological cure, but certain medications, such as stimulants, lithium, and steroids, play a role in alleviating signs and symptoms and reducing the length and frequency of episodes.^1,2

Causes of kleine-levin syndrome

The exact cause of Kleine-Levin syndrome is unknown, but it is thought to be multifactorial. Several potential causal mechanisms have been proposed, though there is still scientific debate surrounding the accuracy of these propositions:³

• Psychological disturbances
• Physical trauma
• Toxins
• Infection
• Abnormalities in pathways involving serotonin and dopamine
• Autoimmunity

Signs and symptoms of kleine-levin syndrome

For the majority of patients with Kleine-Levin syndrome, signs and symptoms develop during adolescence, occurring on average, at 16 years of age. As Kleine-Levin syndrome mostly affects those assigned male at birth, the onset and presentation of the disease in those assigned female at birth is not as well understood.^1,2,3

Flu-like manifestations are commonly reported before the onset of Kleine-Levin syndrome’s characteristic features. These flu-like signs and symptoms often include a general feeling of unwellness, fever, muscle aches, a cough, a sore throat, and nasal congestion.^1-,5

Kleine-Levin syndrome’s signs and symptoms typically occur as episodes lasting from a couple of days to several weeks. These episodes are separated by periods where one doesn’t experience the signs and symptoms they endured during episodes. These periods of normality can last from several weeks to a few months. A patient typically will experience multiple episodes per year but may also experience episodes as sparsely as once per one year and a half.⁴

Kleine-Levin syndrome is characterised by signs and symptoms that occur episodically:⁴

• Hypersomnia or excessive sleepiness, where one may sleep up to 20 hours per day
• Extreme changes in appetite which can be accompanied by rapid weight gain or weight loss
• Difficulty thinking clearly
• Hypersexuality or strong sexual urges
• Disinhibited behaviour

Accompanying the signs and symptoms of Kleine-Levin syndrome may be manifestations of common comorbidities. Anxiety and depression frequently occur in patients with Kleine-Levin syndrome, and so features of these disorders may be present too.⁶

Management and treatment for kleine-levin syndrome

Kleine-Levin syndrome lacks a cure, and management and treatment of the disorder should be specifically tailored to each individual, potentially involving trial and error in establishing the right care. This can involve environmental and lifestyle modifications and medication.

Environmental and lifestyle modifications

A patient’s at-home environment should be modified so the patient is as safe and as comfortable as possible during episodes. For example, with patients sleeping up to 20 hours per day, they must have a place to rest for this period. Furthermore, due to the debilitating nature of Kleine-Levin syndrome’s episodes, making adjustments to the scheduling of school and work and taking leave of absence is often necessary. It is also important that patients refrain from driving and should ideally not be left unattended to wonder about due to the risk of disinhibited behaviour.⁶

Medication 

Certain medications have been shown to play a role in reducing the length and frequency of Kleine-Levin syndrome episodes. Different patients respond differently to various medications, and so finding the right medication for a patient can sometimes involve trial and error.⁷ Some patients may also benefit from medications that not only address episodes but also help alleviate the burden of common comorbidities, such as anxiety and depression.^6,8

Stimulants, such as modafinil, methylphenidate, and amphetamine, can be used to limit excessive sleepiness in patients. For some patients, these medications can increase wakefulness and thus drastically improve their lives, but this is not the case for all patients.^6,9,10

Lithium may be effective in reducing the length and frequency of episodes for many patients with Kleine-Levin syndrome. Furthermore, lithium can help alleviate the bed-riddening impact of Kleine-Levine’s signs and symptoms, helping patients potentially return to some level of normality in their lifestyle.¹¹

Steroids typically are reserved for cases of Kleine-Levin syndrome where the length of episodes exceeds one month and thus are particularly debilitating. Steroids can shorten the length of these episodes. Unlike stimulants and lithium, steroids are administered intravenously and so require a visit to the hospital.¹²

Diagnosis

Making a diagnosis of Kleine-Levin syndrome can occur when in consultation with a doctor, typically a sleep-medicine specialist or neurologist, by going through your patient history. Utilising the Epworth sleepiness scale can help evaluate the severity of a patient’s sleepiness. Diagnostic manuals also provide criteria that can help determine a diagnosis. Furthermore, electroencephalography can be employed to help rule out other diseases which mimic Kleine-Levin syndrome’s signs and symptoms and to subsequently confirm a diagnosis of Kleine-Levin syndrome.¹

Several diseases may need to be ruled out when confirming a diagnosis of Kleine-Levin syndrome:¹

• Depression
• Bipolar disorder
• Narcolepsy
• Klüver-Bucy syndrome
• Temporal lobe epilepsy
• Multiple sclerosis

Patient history

When visiting a doctor, a patient history will likely be taken. This involves a doctor asking you about the onset of the signs and symptoms you’re experiencing and how they have progressed. Through a patient history, a doctor will also be able to gain an understanding of how these signs and symptoms are impacting your day-to-day life. In these consultations, a doctor can also use this time as an opportunity to screen for other diseases that mimic Kleine-Levin syndrome.¹

Epworth sleepiness scale

The Epworth sleepiness scale is a tool that doctors may use to determine the severity of sleepiness a patient is experiencing, particularly how likely it is that a patient will fall asleep in various scenarios. This questionnaire is completed by a patient, commonly in consultations between a patient and a doctor. The results can help the doctor understand how much sleepiness is impacting your life and potentially help determine what treatment is provided later on.¹³

Diagnostic manuals

The third edition of the International Classification of Sleep Disorders provides criteria that are commonly used in diagnosing Kleine-Levin syndrome in consultations between a doctor and patient, where a patient must fulfil every item on the criteria to be diagnosed with this disease:¹⁴

• The patient experiences a minimum of two recurrent episodes of excessive sleepiness and sleep duration that last from two days to five weeks.
• Episodes typically recur multiple times a year and at least once every one and a half years.
• The patient’s alertness, cognitive function, behaviour, and mood are normal between episodes.
• The patient should experience at least one of the following during episodes: cognitive dysfunction, altered perception, disordered eating, or disinhibited behaviour.
• The patient’s signs and symptoms can’t be better explained by another disorder or the use of drugs or medications.

Electroencephalography

Polysomnography, also known as a sleep study, uses electroencephalography (EEG) and can be used to rule out other sleep disorders, particularly narcolepsy, when confirming a diagnosis of Kleine-Levin syndrome.¹⁵ Furthermore, electroencephalography can also help rule out temporal lobe epilepsy.¹⁶

FAQs

How can I prevent kleine-levin syndrome?

As the cause of Kleine-Levin syndrome is still not completely understood, a way to prevent the disease has not been established.³ However, once diagnosed with the disease, some medications, such as lithium and steroids, may prevent episodes from occurring for as long or as frequently in the future.^11,12

How common is kleine-levin syndrome

Kleine-Levin is a rare sleep disorder. The disorder primarily impacts those assigned males at birth and so is even rarer in those assigned females at birth. Ultimately, Kleine-Levin syndrome impacts one to two people per million population.³

Who is at risk of kleine-levin syndrome?

Those assigned male at birth are at a far greater risk of Kleine-Levin syndrome compared to those assigned female at birth, though the disease remains rare across both groups. Adolescents are also likelier to experience the onset of Kleine-Levin syndrome compared to other age groups.³

What can I expect if I have kleine-levin syndrome?

If you have Kleine-Levin syndrome, expect to potentially experience needing to sleep for up to 20 hours per day and have extreme appetite, strong sexual urges, and changes in thinking and behaviour that are unusual for you during episodes.⁴ Expect to need to make changes to your schedule at school or work, not drive, and spend more time in bed.⁶

When should I see a doctor?

With the onset of signs and symptoms, go to see a doctor, as a diagnosis and treatment plan can be established more rapidly this way. Furthermore, seeing a doctor is often needed to take necessary time off of school and work to rest.⁶

Summary

Kleine-Levin syndrome is a rare sleep disorder, having an unknown cause, primarily impacting adolescents assigned male at birth and lasting for decades following onset. This disease can be debilitating, causing excessive sleepiness, extreme appetite, strong sexual urges, as well as other dysfunctional thinking patterns and behaviour, which last from a couple of days to several weeks at a time but are separated by periods of normality. There is not a one-size-fits-all treatment for Kleine-Levin syndrome but treatment is instead tailored to each individual. Treatment can involve environmental and lifestyle modifications, as well as medications. Most patients can expect to eventually see their signs and symptoms resolve, with or without treatment, but a small cluster of patients see no resolution following a couple of decades with the disease.