Kleine-Levin syndrome - Clinicals, Diagnosis, and Management

Neurology

Clinicals - History

Fact Explanation
Introduction Kleine–Levin syndrome (KLS) is a rare sleep disorder that is characterized by features of intermittent hypersomnolence (excessive day time sleepiness) with at least one of the following symptoms such as cognitive or mood disturbances, hyperphagia with compulsive eating, hypersexuality, or abnormal behavior such as irritability, aggression, or personality changes. Though the aetiology of Kleine-Levin syndrome is unknown most people have an upper respiratory tract infection prior to the symptoms of Kleine–Levin syndrome suggesting an immunological pathology leading to the leading to hypothalamic dysfunction. It is suggested that neurotransmitters like serotonin, dopamine, and orexin (hypocretin) may also play a role in the pathogenesis. Nature of the disease is benign and has a tendency to resolve spontaneously. Introduction
Kleine–Levin syndrome (KLS) is a rare sleep disorder that is characterized by features of intermittent hypersomnolence (excessive day time sleepiness) with at least one of the following symptoms such as cognitive or mood disturbances, hyperphagia with compulsive eating, hypersexuality, or abnormal behavior such as irritability, aggression, or personality changes. Though the aetiology of Kleine-Levin syndrome is unknown most people have an upper respiratory tract infection prior to the symptoms of Kleine–Levin syndrome suggesting an immunological pathology leading to the leading to hypothalamic dysfunction. It is suggested that neurotransmitters like serotonin, dopamine, and orexin (hypocretin) may also play a role in the pathogenesis. Nature of the disease is benign and has a tendency to resolve spontaneously.
Abnormalities in the sleep pattern There are episodes of recurrent hypersomnia, with inbetween periods of normal behavior. It has intermittent and periodic nature. There is a difficultty in waking in the early stages of the symptomatic period, but latter they may appear to be resting or awake with their eyes closed. They have an excessive daytime sleepiness, despite sleeping anywhere from 12 to 21 hours per day. Abnormalities in the sleep pattern
There are episodes of recurrent hypersomnia, with inbetween periods of normal behavior. It has intermittent and periodic nature. There is a difficultty in waking in the early stages of the symptomatic period, but latter they may appear to be resting or awake with their eyes closed. They have an excessive daytime sleepiness, despite sleeping anywhere from 12 to 21 hours per day.
Duration of the symptoms Each episode is of brief duration and duration of an one episode may be from a week to 1–2 months. In between they are totally symptom free. Duration of the symptoms
Each episode is of brief duration and duration of an one episode may be from a week to 1–2 months. In between they are totally symptom free.
Age Teenage boys are commonly affected. Age
Teenage boys are commonly affected.
Hypersexuality This is common in boys than in girls. Increased sexual drive, sexual comments, unwanted sexual advances, and frequent masturbation is observed among these boys. Hypersexuality
This is common in boys than in girls. Increased sexual drive, sexual comments, unwanted sexual advances, and frequent masturbation is observed among these boys.
Abnormal behavior Person may become aggressive towards the others, there can be associated personality changes. Abnormal behavior
Person may become aggressive towards the others, there can be associated personality changes.
Hyperphagia They eat a lot compulsively, particularly they favor sweets. They usually do not care about the amount of the food that they consumed. Hyperphagia
They eat a lot compulsively, particularly they favor sweets. They usually do not care about the amount of the food that they consumed.
Lethargy, apathy and poor memory As they have excessive day time sleepiness, While awake, they tend to be often apathetic, and lethargic. Lethargy, apathy and poor memory
As they have excessive day time sleepiness, While awake, they tend to be often apathetic, and lethargic.
Forgetfullness Excessive daytime sleepiness, will cause impairment in communication, concentration, and memory. Forgetfullness
Excessive daytime sleepiness, will cause impairment in communication, concentration, and memory.
Abnormal feelings They experience “déjà vu” during episodes, where they feel as if they are in a dream-like state or experiencing life outside of their own bodies. Abnormal feelings
They experience “déjà vu” during episodes, where they feel as if they are in a dream-like state or experiencing life outside of their own bodies.
Interpersonal communication They tend to socially withdrawn, and executive functioning and communication skills may be poor. Interpersonal communication
They tend to socially withdrawn, and executive functioning and communication skills may be poor.
Reduced productivity of work Excessive daytime sleepiness, will cause impairment in communication, concentration, and memory will affect the day today work. Reduced productivity of work
Excessive daytime sleepiness, will cause impairment in communication, concentration, and memory will affect the day today work.
Triggering factors Sleep-deprivation, trauma, alcohol consumption may be the precipitating factors for the diseases. Triggering factors
Sleep-deprivation, trauma, alcohol consumption may be the precipitating factors for the diseases.

Clinicals - Examination

Fact Explanation
Mood As they have excessive day time sleepiness, while awake, they tend to be often apathetic, and lethargic. They will be depressed and anxious at times. Mood
As they have excessive day time sleepiness, while awake, they tend to be often apathetic, and lethargic. They will be depressed and anxious at times.
Irritability They will have associated behavioural abnormalities such as irritability and aggressiveness. Irritability
They will have associated behavioural abnormalities such as irritability and aggressiveness.
Poor memory and concentration Excessive daytime sleepiness, will cause impairment in communication, concentration, and memory. Memory deficit may be related to the impaired new learning, registering, unable to focus attention on particular event etc. It may be either short or long-term memory deficit. Poor memory and concentration
Excessive daytime sleepiness, will cause impairment in communication, concentration, and memory. Memory deficit may be related to the impaired new learning, registering, unable to focus attention on particular event etc. It may be either short or long-term memory deficit.
Altered perception Pain insensitivity. may cause impaired sensations such as temperature sensation. Altered perception
Pain insensitivity. may cause impaired sensations such as temperature sensation.
Hypersexuality Boys show an increased sexual drive, and frequent masturbation. Hypersexuality
Boys show an increased sexual drive, and frequent masturbation.
Abnormal behaviour Repetitive or compulsive behaviors, aggressive behaviours are comon in tehse children. Words may be rude, offensive, and in sexually charged language. Abnormal behaviour
Repetitive or compulsive behaviors, aggressive behaviours are comon in tehse children. Words may be rude, offensive, and in sexually charged language.
Insight Though they are aware about the abnormal behaviour, they are hesitant to discuss their symptoms as they are ashamed of it once resumed to normal behaviour. Insight
Though they are aware about the abnormal behaviour, they are hesitant to discuss their symptoms as they are ashamed of it once resumed to normal behaviour.
Changes in blood pressure and heart rate Transient autonomic dysfunction is in some occasions. Changes in blood pressure and heart rate
Transient autonomic dysfunction is in some occasions.

Investigations - Diagnosis

Fact Explanation
Electroencephalography EEG will show generalized slowing of drowsiness in up to 70% of cases during episodes. Electroencephalography
EEG will show generalized slowing of drowsiness in up to 70% of cases during episodes.
Polysomnography (PSG) First half of the symptomatic period will demonstrate a decrease in slow wave sleep, and second half of the symptomatic period will demonstrate decrease in REM sleep. These changes are not found in each and every patient. Polysomnography (PSG)
First half of the symptomatic period will demonstrate a decrease in slow wave sleep, and second half of the symptomatic period will demonstrate decrease in REM sleep. These changes are not found in each and every patient.

Investigations - Management

Fact Explanation
Sleep diary Is important to monitor the response to treatment. Sleep diary
Is important to monitor the response to treatment.
Polysomnography This is particularly important when the patient is not responding to the treatment, symptom severity increasing or new symptoms are appearing. Polysomnography
This is particularly important when the patient is not responding to the treatment, symptom severity increasing or new symptoms are appearing.
Cerebrospinal fluid (chemistry, microscopy, and culture If the patient is presenting with drowsiness, ruling out the cerebral infections is of value. Cerebrospinal fluid (chemistry, microscopy, and culture
If the patient is presenting with drowsiness, ruling out the cerebral infections is of value.
Thyroid function tests and antinuclear antibodies Important to rule out the hypothyroidism as a cause of excessive sleepiness. Thyroid function tests and antinuclear antibodies
Important to rule out the hypothyroidism as a cause of excessive sleepiness.
Liver and renal function tests Drugs may alter these functions and need to check before the treatment. Liver and renal function tests
Drugs may alter these functions and need to check before the treatment.
Low CSF hypocretin-1 Low CSF hypocretin-1 is highly specific (99.1%) and sensitive (88.5%) for detecting other sleeping disorders narcolepsy with cataplexy that may cause diagnostic confusion. Kleine-Levin syndrome will mostly show the normal levels of CSF hypocretin-1 levels. Low CSF hypocretin-1
Low CSF hypocretin-1 is highly specific (99.1%) and sensitive (88.5%) for detecting other sleeping disorders narcolepsy with cataplexy that may cause diagnostic confusion. Kleine-Levin syndrome will mostly show the normal levels of CSF hypocretin-1 levels.
Magnetic Resonance Imaging of the brain Hypothalamic structural abnormality need to be ruled out. Magnetic Resonance Imaging of the brain
Hypothalamic structural abnormality need to be ruled out.
Polysomnography This will be helpful to rule out the other similar sleeping disorders. Idiopathic hypersomenence shows the features of shortened sleep latency, increased total sleep time and a normal sleep architecture. Polysomnography
This will be helpful to rule out the other similar sleeping disorders. Idiopathic hypersomenence shows the features of shortened sleep latency, increased total sleep time and a normal sleep architecture.

Management - Supportive

Fact Explanation
Patient education Education of the patient should involves the benign nature of the disease, potential complications, treatment strategies and its side effects. Patient education
Education of the patient should involves the benign nature of the disease, potential complications, treatment strategies and its side effects.
Sleep hygiene techniques Sleep diary information with subjective sleep hours and activities are required to identify the extent of the problem. Sleep hygiene techniques
Sleep diary information with subjective sleep hours and activities are required to identify the extent of the problem.
Avoiding triggers and high risk situations are the triggers that can aggravate the condition and needed to be avoided. High risk jobs such as driving, working at height and machinery work may be dangerous as they are getting episodes of hypersomnia. Avoiding triggers and high risk situations
are the triggers that can aggravate the condition and needed to be avoided. High risk jobs such as driving, working at height and machinery work may be dangerous as they are getting episodes of hypersomnia.
Follow up Monitoring the severity of the disease with sleep diary and assesing the side effects of the treatment is important. Follow up
Monitoring the severity of the disease with sleep diary and assesing the side effects of the treatment is important.

Management - Specific

Fact Explanation
Treating the excessive sleepiness with stimulants Stimulants may be used to treat the excessive sleepiness. Eg:- Modafinil, amphetamine, desamphetamine and methylphenidate. It acts to shorten the symptomatic period. Treating the excessive sleepiness with stimulants
Stimulants may be used to treat the excessive sleepiness. Eg:- Modafinil, amphetamine, desamphetamine and methylphenidate. It acts to shorten the symptomatic period.
Antipsychotics and mood stabilizers Antipsychotics and mood stabilizers are also used on certain occasions. eg:- lithium and carbamazepine etc. As there are some similarities between KLS and affective disorders, lithium and carbamazepine are beneficial in some cases. These drugs may increase irritability and do not improve cognitive and behavioral disturbances. But lithium may have an effect on controlling the behavioural symptoms. Antipsychotics and mood stabilizers
Antipsychotics and mood stabilizers are also used on certain occasions. eg:- lithium and carbamazepine etc. As there are some similarities between KLS and affective disorders, lithium and carbamazepine are beneficial in some cases. These drugs may increase irritability and do not improve cognitive and behavioral disturbances. But lithium may have an effect on controlling the behavioural symptoms.
Macrlides Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter acting to regulate the sleep/wake cycle regulation. Clarithromycin, is a macrolide antibiotic that inhibits the bacterial protein synthesis, but also functioning as a GABAA receptor antagonist. Therefore it is used for the treatment of patients with Kleine-Levin syndrome. Macrlides
Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter acting to regulate the sleep/wake cycle regulation. Clarithromycin, is a macrolide antibiotic that inhibits the bacterial protein synthesis, but also functioning as a GABAA receptor antagonist. Therefore it is used for the treatment of patients with Kleine-Levin syndrome.

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