Introduction  

Sleep is a bodily process that enables the brain and the body to rest, which is important for mental and physical health. This ensures that the body remains in homeostasis to maintain the body's overall health. However, sleeping disorders are complications that can lead to an increase in morbidity. A rare but profoundly disruptive condition is Kleine-Levin Syndrome (KLS). It is a neurological disorder where patients may sleep up to 20 hours a day, characterised by recurrent episodes of hypersomnia, cognitive and behavioural disturbances. This article will talk about sleeping patterns associated with KLS, prolonged sleep cycles, and their physiological and psychological implications.^1,2

Kleine-levin syndrome (KLS)

KLS is a rare neurological condition that is a form of recurrent hypersomnia. The estimated prevalence is 1 to 5 cases per million people worldwide. Due to the rare states and overlapping symptoms with psychiatric and neurological conditions, it is commonly underdiagnosed or misdiagnosed. Therefore, it can result in an underestimation of its true prevalence.³

Individuals present behavioural symptoms, psychomental changes and hyperphagia. It commonly affects adolescents, typically people assigned male at birth (AMAB) (approximately 70% of cases), and the average age of onset is between 15 and 19 years. However, people assigned female at birth (AFAB) with KLS often exhibit longer episode durations and more frequent cognitive disturbances.^4,5,6

KLS is reported across all ethnic and geographic populations. However, some studies suggest a slightly higher occurrence in individuals of Ashkenazi Jewish descent, indicating a possible genetic predisposition in certain groups.⁷ 

Aetiology and pathophysiology

Although the cause of KLS is unknown, growing evidence has supported the hypothesis of hypothalamic dysfunction as a contributing factor in the pathophysiology of the syndrome. The hypothalamus plays a critical role in regulating sleep, appetite, body temperature, and hormonal cycles. Therefore, a dysfunction in the hypothalamus presents disruptions in these systems for KLS patients. 

This can be identified from neuroimaging studies such as magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. These scans generally indicate reduced blood flow in the thalamus, hypothalamus, and frontal lobe of the brain. Such abnormalities are usually identified during the time the patient exhibits symptoms linked to those specific brain regions.

Furthermore, environmental and physiological triggers can be present alongside KLS episodes, such as:

• Infections, for example, upper respiratory tract infections
• Psychological stress
• Sleep deprivation
• Physical trauma
• Head injuries

These symptoms can be due to autoimmune or post-infectious mechanisms; however, further research is required on this. 

Other disturbances can be cognitive, such as memory deficits, slow comprehension and thinking. They are presented alongside hyperphagia (compulsive overeating), hypersexuality, and derealisation. These symptoms can be presented in both patients and caregivers, which can make the management more difficult.^5,8,9

Characteristics of hypersomnia in KLS

Hypersomnia is a hallmark symptom where patients sleep around 16 to 20 hours per day. It can either be a sudden onset or an episodic pattern; however, it can last for a few days to weeks. For KLS patients, it is commonly noticed to last for 1-3 weeks. Symptoms include drowsiness and inability to remain awake, which can impact daily life. They may struggle to eat, stay clean or even communicate with others.¹⁰

This happens because of improper regulation within the brain's sleep-wake circuitry, which includes the thalamus, hypothalamus, and associated thalamocortical pathways. These structures play a crucial role in regulating the circadian rhythm and sustaining consciousness. Compared to other hypersomnias, KLS is distinct. It involves prolonged sleep periods, whereas idiopathic hypersomnia presents as chronic and persistent sleepiness without complete return to normalcy.^11,12 

Prolonged sleep cycles and circadian rhythms

Polysomnography is a sleep study that can be used to observe individuals' rapid eye movement (REM) and non-rapid eye movement (NREM) sleep cycles. These abnormalities play a role in prolonged sleep. A diagnostic tool such as electroencephalography (EEG) can help identify the absence of normal sleep spindles. One contributing factor is melatonin secretion, which is a hormone that is responsible for circadian timing. Alongside this, other symptoms such as fatigue and cognitive dysfunction can result in short-term memory impairment, concentration difficulties and more.¹³

Diagnostic and monitoring tools 

Polysomnography and EEG

Polysomnography and EEG are commonly used to examine an individual's sleep patterns and brain activity. It can help to tell if there is an atypical activity, such as reduced REM sleep or any absence of normal sleep spindles.¹⁴ 

Sleep diaries and actigraphy

Sleep diaries and actigraphy can be used to track the beginning, duration and frequency of the episodes over time. Helps to understand the individual sleep patterns and identify any sleep disorders alongside KLS.¹⁵ 

Neuroimaging studies

Neuroimaging studies include functional MRI (fMRI) and positron emission tomography (PET) scans. It can be used to find any structural or functional abnormalities in the brain that are responsible for sleep regulation and consciousness.¹⁶ 

Differential diagnosis

Individuals with KLS are frequently misdiagnosed with a mental health disorder. The episodes of excessive sleepiness, increased appetite, and social disengagement can resemble major depression, and some individuals undergo a short phase of heightened energy after these episodes, resembling a manic episode. Conditions can include bipolar disorder, depression, narcolepsy and epilepsy.⁶

Research gaps and future directions

Despite the increasing public awareness of KLS, there are still some gaps that need further investigation. One limitation is the difficulty in pinpointing the exact cause of the syndrome in individual cases, which makes it challenging to develop targeted treatments for a cure. While neuroimaging indicates that dysfunction in the hypothalamus and thalamus may play a role, the precise mechanisms that trigger hypersomnia and other related symptoms remain uncertain. 

Another obstacle is the lack of established diagnostic criteria and a global consensus. This inconsistency leads to variations in research and treatment practices worldwide. Consequently, accurate global prevalence data is not available, and many cases may go unrecognised. 

Future studies should focus on integrating objective diagnostic methods, elucidating the pathophysiological mechanisms, and creating targeted therapies. This approach could facilitate early diagnosis and help avoid misdiagnosis.¹⁷ 

Summary

Sleep is essential for mental and physical health, helping the body maintain balance, or homeostasis. However, sleep disorders can lead to serious health issues. One such disorder is Kleine-Levin Syndrome (KLS), a rare neurological condition characterised by excessive sleep, where individuals may sleep up to 20 hours a day and experience cognitive and behavioural changes. KLS is categorised as recurrent hypersomnia, affecting an estimated 1 to 5 people per million. It is often misdiagnosed due to its overlapping symptoms with other conditions, leading to a lower recognition of its prevalence. It primarily affects adolescents, especially those assigned male at birth, with an average onset between 15 and 19 years. People assigned female at birth usually have longer episodes and more cognitive disturbances.

The cause of KLS remains unknown, but there is evidence that hypothalamic dysfunction may play a role. The hypothalamus regulates sleep, appetite, and body temperature, and disruptions in this area can lead to symptoms of KLS. Neuroimaging studies show reduced blood flow in brain areas associated with sleep regulation during episodes. Environmental factors such as infections, stress, sleep deprivation, and physical trauma may trigger episodes. Other symptoms accompanying KLS can include memory issues, slow thinking, compulsive overeating, hypersexuality, and feelings of unreality, complicating the management of the disorder. A defining feature of KLS is hypersomnia, where patients sleep around 16 to 20 hours daily, with episodes lasting from a few days to weeks. Victims may face challenges in daily activities due to excessive drowsiness, affecting their ability to communicate or care for themselves.

KLS differs from other sleep disorders, as it involves significant sleep periods rather than persistent sleepiness. Diagnostic tools for KLS include polysomnography and EEG to check sleep patterns and brain activity. Sleep diaries and actigraphy are useful to track sleep episodes, while neuroimaging studies help locate brain abnormalities related to sleep. However, diagnosing KLS is complicated by its similarity to other conditions like bipolar disorder and narcolepsy. There are gaps in research, particularly concerning its exact causes, diagnostic criteria, and targeted treatments, highlighting the need for further studies to improve understanding and management of KLS.

FAQs

What is kleine-levin syndrome (KLS)?

A rare neurological condition that can impact an individual's daily life due to extreme hypersomnia. This is when individuals sleep for an excessive period of time, for around 20 hours per day. This can cause cognitive and behavioural disturbances. It typically affects adolescents, more males than females. 

What causes KLS?

There is no identified cause for KLS; however, neurological studies have shown that hypothalamic and thalamic dysfunction are contributing factors. Other factors, such as stress, viral infections, and sleep deprivation, can trigger the syndrome to occur. However, further research is required to occur to understand the condition for accurate treatment. 

What are the main symptoms of KLS?

The main symptom is hypersomnia. However, there are other symptoms such as memory loss, slow thinking and confusion, hyperphagia and hypersexuality, depression and anxiety. 

How long do KLS episodes last?

Around 1 to 3 weeks, sometimes months.

How is KLS diagnosed?

Typically, Polysomnography,  EEG, sleep diaries, neuroimaging and more. 

Is there a cure?

No identified cure yet; however, there are both pharmacological and non-pharmacological treatments. Including modafinil, mood stabilisers like lithium and CBT.

Can it be misdiagnosed?

Yes, due to overlapping symptoms of depression and anxiety.