What Is Kleine-Levin Syndrome?
What Is Kleine-Levin Syndrome? KLS is a disease of adolescence, and sometimes will begin after infection or illness, says Tom Rico of the Center for Narcolepsy & KLS Research at Stanford University, California.”An individual with KLS will have sleep episodes, typically lasting between one and three weeks, with coinciding cognitive disturbance in the few hours of wakefulness.”During this time period, a patient will sleep anywhere between 16 to 22 hours a day, every day, until the conclusion of the episode.”But the excessive sleeping is only half the problem, he says, because when awake during the episode, patients experience what they describe as a “dream-like state”.
Kleine–Levin syndrome (KLS), also known as Sleeping Beauty syndrome, is a rare sleep disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Many patients also experience hyperphagia, hypersexuality and other symptoms. Patients generally experience recurrent episodes of the condition for more than a decade. Individual episodes generally last more than a week but less than a month. The condition greatly affects the personal, professional, and social lives of sufferers, but symptoms spontaneously resolve and seldom cause permanent issues.
The severity of symptoms and the course of the syndrome vary between sufferers. Patients commonly have about 20 episodes over about a decade. Several months generally elapse between episodes. The onset of the condition usually follows a viral infection; several different viruses have been observed to trigger KLS. It is generally only diagnosed after similar conditions have been excluded; MRI, CT scans, lumbar puncture, and toxicology tests are used to rule out other possibilities. The syndrome’s mechanism is not known, but the thalamus is thought to possibly play a role. Tomography has shown hypoperfusion in the brains of patients during episodes.
KLS is very rare, occurring at a rate of one in a million, which limits research into genetic factors. The condition primarily affects adolescent males, though females can also be affected and the age of onset varies. There is no known cure, and there is little evidence supporting drug treatment. Lithium has been reported to have limited effects in case reports, decreasing the length of episodes and duration between them in some patients. Stimulants have been shown to promote wakefulness during episodes, but they do not counteract cognitive symptoms or decrease the duration of episodes. The condition is named after Willi Kleine and Max Levin, who described cases of the disease in the early 20th century. It was added to the International Classification of Sleep Disorders in 1990.
Patients with Kleine–Levin syndrome (KLS) experience reoccurring feelings of excessive tiredness and prolonged sleep (hypersomnia). In most cases, patients sleep 15 to 21 hours a day during episodes. Excessive appetite (hyperphagia) and unusual cravings are present in half to two thirds of cases. About half of patients, mainly male patients, experience dramatically increased sexual urges (hypersexuality). Several other symptoms usually accompany the syndrome, including marked changes in mood and cognitive ability. Derealization and severe apathy are present in at least 80 percent of cases.
About one third of patients experience hallucinations or delusions. Depression and anxiety occur less commonly; one study found them in about 25 percent of patients. Individuals usually cannot remember what happened during episodes. Repetitive behaviors and headaches are commonly reported. Some patients act very childlike during episodes, and communication skills and coordination sometimes suffer. In some cases, the autonomic nervous system malfunctions as well.
Sleep studies of KLS show varying results based on the amount of time the patient is observed. Slow wave sleep is often reduced at the beginning of episodes, and REM sleep is reduced near the end. Conversely, REM sleep is often normal at the beginning, and slow wave sleep is often normal by the conclusion. Stage two non-rapid eye movement sleep is often interrupted during KLS. Studies also show that stage one and three non-rapid eye movement sleep become more efficient when the episodes end. The Multiple Sleep Latency Test has yielded inconsistent results when given to KLS patients. In many cases, hours are spent in a withdrawn sleep-like state while awake during episodes. Most sleep studies have been performed while subject are near the end of their episodes. Some patients experience brief insomnia and become very happy and talkative after the episode ends.
The first time a patient experiences KLS, it usually occurs along with symptoms that are similar to those of the flu or encephalitis. In at least 75 percent of cases, symptoms occur after an airway infection or a fever. Viruses observed before the development of the condition include Epstein-Barr virus, varicella zoster virus, herpes zoster virus, Influenza A virus subtypes, and adenovirus. Several days after symptoms first occur, patients become very tired.
In cases that occur after an infection, KLS usually starts within three to five days for teenagers and fewer for children. In other cases, alcohol consumption, head injury, or international travel precede symptoms. Lifestyle habits, such as lack of sleep and stress, have also been proposed as possible triggers. First episodes of KLS are preceded by a clear event in about 90 percent of cases. Recurrences generally do not have clear triggers; only about 15 percent have a precipitating event.
The condition generally disrupts the social lives and academic or profession obligations of sufferers. Some patients also gain weight during episodes. The most severe cases cause a long-term impact on mood and cognitive attention. In rare cases, patients experience long-term memory problems.
In patients with KLS, MRI and CT scans show normal brain morphology. When SPECT is performed, hypoperfusion can often be observed in the brain, particularly in the thalamic and frontotemporal areas. The hypoperfusion is significantly diminished between episodes. Serum biology, c-reactive proteins and leptins, the hormonal pituitary axis, and protein in the cerebral spinal fluid (CSF) are normal in KLS patients.
It is not known what causes KLS, but several mechanisms have been proposed. One possible explanation is hypothalamic or circadian dysfunction. The thalamus probably plays a role in the out-of-control sleeping, and patients with diencephalic–hypothalamic dysfunction caused by tumors experience symptoms similar to those of KLS patients. Specifically, the medial temporal regions of the thalamus may be involved, although examinations of KLS patients have not consistently found abnormalities in this area.
The temporal lobe also appears to play a role in the condition, possibly causing cognitive difficulties. The apathy and disinhibition found in some KLS sufferers suggest that the condition may include frontal lobe dysfunction as well. The involvement of the thalamus, temporal lobe, and frontal lobe of the brain suggests that there is a multifocal, localized encephalopathy. There are also persistent subclinical abnormalities in KLS sufferers.
Another possible explanation concerns the metabolism of serotonin and dopamine. An imbalance in the neurotransmitter pathways of these chemicals could play a role. Viral infections have also been suggested as a possible cause. Evidence for their role includes lesions found in autopsies. CSF samples from KLS patients indicate that the condition has a different cause than influenza-associated encephalopathy. Triggers of KLS may also affect the blood-brain barrier, which could play a role in the condition. There is limited evidence of what role hypocretin may play, although it often influences hypersomnia.
Androgen might (indirectly) block melatonin receptors, possibly by mean of vasodilation, and cause cholinergic abnormalities in some cases of Kleine–Levin syndrome. Because KLS occurs at a much higher rate in Jews and in some families, it is likely that there is some genetic component in addition to environmental factors. Genetic studies hold promise for understanding the disease, but they have yielded inconsistent results and few patients are available for testing. Epilepsy and depression do not appear to cause KLS. The condition’s rapid onset after infections indicates that the immune system is not to blame.