by Gerard Meskill, M.D.
A 15-year-old boy came to the Stanford Sleep Center complaining of episodes of excessive sleepiness associated with disturbed behavior that started one year prior. He went to school one day and began picking at his face. He did not respond to questions when asked. He walked over to the volleyball court and just stood there staring blankly. He appeared disoriented. When his mother came to the school to bring him to the hospital, he did not recognize her. Once arriving in the emergency department, he went to sleep. He woke up an hour later feeling better. Two days later at home, he began sleeping more. When awake, he ate constantly and would just stare blankly. He used strange voices and had unusual movements.
Suspicious for seizures, his doctor performed an electroencephalogram (EEG), but this was normal. His neurologist thought the symptoms were psychological and sent him to a psychiatrist. The psychiatrist thought they were neurological and sent him back to the neurologist. Finally, his aunt saw a television special on a rare sleep disorder, called Kleine-Levin Syndrome (KLS). The family brought this information to the neurologist, and the diagnosis was confirmed.
KLS is a rare sleep disorder that mainly affects teenage boys, though cases have been reported in girls and adults. There is no test to confirm the presence of the disorder, so all diagnoses are made based on the clinical presentation of the illness.
The hallmark feature of the disorder is episodes of extreme sleepiness that may come and go. Typically, these episodes occur a few times per year and each episode lasts days to weeks. During these attacks of sleepiness, the affected person will sleep for most of the day. It is not uncommon for these people to sleep more than 20 hours per day. When they are awake, they will exhibit other strange behaviors and signs, such as binge eating, hypersexuality, aggression, confusion and even hallucinations. Often they report later that everything seemed "dream-like" or "not real" during the episode (known as "derealization" episodes). Between episodes, these individuals behave and sleep normally. After several years of recurring events, eventually the disease resolves spontaneously.
No one is sure what causes KLS, though several theories exist currently. Proposed triggering mechanisms include infections or fever, substance abuse (in particular alcohol and marijuana), head trauma, sleep deprivation, stress and even menses. More recently, an autoimmune mechanism has been proposed, similar to what is known to cause multiple sclerosis, lupus, rheumatoid arthritis and many other diseases. In one study, a specific gene found in European patients with KLS led to a two-fold increased risk of developing the disease.
A more recent study conducted in Taiwan demonstrated a possible connection between certain kinds of infections and the incidence of KLS attacks. The study looked at 30 patients with KLS between 2005 and 2006, and it demonstrated that almost 97 percent of all initial episodes of KLS symptoms occurred after upper respiratory tract infections (URIs), fever, or encephalitis. A similar pattern also was found when retrospectively studying cases from 2004 and 2005. Since infections trigger our immune response, these findings support the hypothesis that KLS is an autoimmune process.
The part or parts of the brain that causes KLS is also unknown, though there have been many interesting studies that have led to compelling theories. A few studies have used single photon emission computerized tomography (SPECT) to compare blood flow patterns in the brain during a KLS episode and an asymptomatic period. Although several brain structures showed a relative decrease in blood flow in some patients during a KLS attack, almost all patients showed a significant decrease in flow in the thalamus. The thalamus is a deep structure in the brain responsible for relaying information to other parts of the brain and the spinal cord. It has been demonstrated to be the gatekeeper of consciousness during sleep. In a few case reports, a stroke affecting only the thalami has caused persistent apathetic behavior, increased sleepiness, hypersexuality, and aggressiveness. These are all traits also exhibited by patients with KLS, supporting the association.
Treatment for KLS mainly is supportive. Several drug trials have been attempted without much benefit and in controlled long-term studies has not been shown to prevent relapse. Fortunately, aside from some evidence of mild impairment of working memory demonstrated in neuropsychological testing in individuals that keep having repetitive attacks during adulthood, symptoms resolve with time and attacks wane in frequency with age.
Gerard Meskill, M.D. is a sleep medicine fellow at the Stanford Center for Sleep Sciences and Medicine. This Center is the birthplace of sleep medicine and includes research, clinical, and educational programs that have advanced the field and improved patient care for decades. Dr. Meskill has also been trained in neurology and plans to practice in Houston, Texas beginning in July 2013. To learn more, visit us at: http://sleep.stanford.edu/.
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