Kleine-Levin Syndrome
Kleine-Levin Syndrome
Definition
Kleine-Levin syndrome (also known as KLS) is a rare disorder. The most prevalent characteristic of the syndrome is recurring periods of excessive drowsiness and sleep (up to 20 hours per day) that can last weeks.
Description
KLS was first described in 1862 and is considered extremely rare, with only 27 cases reported from 1962 to 2004 in the United States. In addition to excessive drowsiness, an episode of KLS can also involve hypersexuality and compulsive behaviors, including compulsive eating. It usually first manifests in adolescence and appears to lessen and resolve on its own with age. Although cognitive and behavioral disturbances, including transient confusion and memory deficits, can accompany the disorder, there appear to be no lasting, permanent effects. In addition to other manifestations, KLS can be accompanied by mood disorders and an extreme irritability that translates into violent behaviors in atypical cases.
The average number of episodes of KLS among cases is seven, each lasting a median 10 days about every 3.5 months. The median length of time a person experiences the syndrome is eight years, although this time is longer in women and in people who experience less frequent episodes in their first year following onset.
Causes and symptoms
Most studies suggest that KLS is related to the hypothalamus, the organ in the brain that governs appetite, sleep, and hormone cycles, among other things. Researchers have failed to identify specific causes of KLS, although there are some apparent associations between events preceding the first episode of the disorder and its manifestation. The majority of cases are isolated, meaning that they do not appear to have a heritable basis.
Because many people with KLS experienced a viral illness just prior to their first episode, some experts propose that the causative agent is a type of viral or post-autoimmune encephalitis that affects the hypothalamus. Reported infections included tonsillitis, nonspecific flu-like fever, upper respiratory tract infection, and gastroenteritis. One study revealed that three of four autopsied patients with KLS had signs of inflammatory encephalitis in the hypothalamus.
Despite the suggested involvement of the hypothalamus, no association has been found clinically between a KLS episode and changes in hypothalamic hormones, cerebrospinal fluid, or other neurological signs. Similarly, in spite of symptoms such as hypersexuality, there have been no identified related changes in sex steroid hormones. One clinical association with KLS that has been found in 70% of patients is a nonspecific slowing of background brain activity on electroencephalogram testing. All magnetic resonance imaging (MRI) andcatscan (CT) imaging of the brain in KLS cases has been normal.
Symptoms can last weeks or even months. In addition to hypersomnia (excessive sleepiness), symptoms can include excessive eating without regard to content or quantity, extreme irritability, disorientation and confusion, low energy or no energy, hypersensitivity to noise, disconnection from reality, and blurred vision. A person experiencing a KLS episode may also report hallucinations. The abnormally uninhibited sex drive associated with some KLS episodes occurs more frequently in males and manifests in ways that can be alarming: those affected may expose themselves and make unwanted sexual advances. The disorder is episodic, and affected people behave normally between episodes. Intervals between episodes can sometimes last years.
Although an episode can come on without much warning, there are sometimes prodromal (pre-occur-rence) signs that a KLS event is impending, especially a feeling of sudden, overwhelming tiredness. The excessive drowsiness of a KLS episode precludes normal participation in activities. In spite of the hypersomnia, a person experiencing a KLS episode is still able to wake to eat or void.
There may be some depression or amnesia after an attack. Depression can accompany KLS and an episode of KLS can occur with a recurring episode of depression. About half of patients report a depressive mood in conjunction with a KLS event.
KLS can occur as the primary disease, with onset in the teen years, or it can occur secondary to another disease or health problem, such as multiple sclerosis or brain trauma. Although fewer cases of secondary KLS occur compared to primary KLS, patients with secondary
KEY TERMS
Hypersexuality —A clinically significant level of desire to engage in sexual behaviors.
Hypersomnia —Excessive sleepiness.
Hypothalamus —The hypothalamus is part of the brain that links the nervous and endocrine systems and also governs emotion, sexual activity, body temperature, hunger, thirst, and sleep cycles.
KLS may experience much longer and more frequent episodes.
Demographics
There are no published population-based studies reporting KLS incidence. Age at onset is usually in the late teens, and the syndrome is four times more common in males. The average age at onset is about 16.9 years, with a range from 4 to 82 years. About 81%of cases start in the preteen and teen years. Although it occurs more often in males, symptoms may be worse or the disease longer lasting in females.
Diagnosis
According to one source, diagnosing KLS is an difficult process and can result in an average delay of four years before a patient receives the correct diagnosis.
Treatments
No definitive treatment for KLS exists, and response to current treatments can be limited. A clinician can try to address the excessive sleepiness using orally administered stimulants (amphetamines, methylphenidate , modafinil). Because there are crossover characteristics between KLS and other mood disorders, lithium or carbamazepine are sometimes prescribed, and lithium appears to have some beneficial effect on relapse rates in a little less than half of the cases.
Prognosis
Excluding quality-of-life issues, KLS is a benign disorder that usually improves or resolves with age without permanent effects on intellect or physical function.
Prevention
Because the causes of KLS are undefined, prevention measures have not been identified.
Resources
PERIODICALS
Arnulf, I., J.M. Zeitzer, J. File, N. Farber, and E. Mignot, “Kleine-Levin syndrome: a systematic review of 186 cases in the literature.” Brain 128(2006): 2763–2776.
ORGANIZATION
NINDS Kleine-Levin Syndrome Information Page. Available online at <http://www.ninds.nih.gov/disorders/kleine_levin/kleine_levin.htm> (accessed 01/07/07).
Kleine-Levin Syndrome Foundation, P.O. Box 5382, San Jose, CA, 95150-5382. (408) 265-1099. <http://www.klsfoundation.org/site/kls/>.
National Organization for Rare Disorders (NORD), P.O. Box 1968, 55 Kenosia Avenue, Danbury, CT, 06813-1968. (203) 744-0100. <http://www.rarediseases.org>.
National Sleep Foundation, 1522 K Street NW, Suite 500, Washington, D.C. 20005. (202) 347-3471. <http://www.sleepfoundation.org>.
Emily Jane Willingham, Ph.D.