Kleine-Levin syndrome (KLS) is a rare disorder in which affected people experience episodes at least once per year during which they sleep for at least 11 hours out of every day (but often for days at a time), eat excessively (megaphagia), have abnormal thinking and behavior, and hypersexuality. Between episodes, their alertness, behavior, and thinking are normal.
Both the International Classification of Sleep Disorders and the Diagnostic and Statistical Manual of Mental Disorders include criteria to diagnose KLS, but there are no biomarkers—no substances in the body that can be measured—that can help doctors in making the diagnosis of KLS. Some scientists who study KLS think that KLS is caused by something in the immune system that makes the part of the brain called the hypothalamus not work properly. Nerve cells (neurons) in the hypothalamus produce two neurotransmitters, hypocretin and histamine, that are involved in regulating alertness, feeding, and neuroendocrine and autonomic function.
Who Were the Researchers?
Dr. Yves Dauvilliers and his colleagues in Montpellier, France, have a large sleep clinic in which they specialize in the treatment of various forms of hypersomnia.
Who Were the Research Subjects?
This research was performed on two males aged 13 and 16 years with typical symptoms of KLS.
What Did The Researchers Do?
The researchers performed lumbar punctures and removed cerebrospinal fluid (CSF) in the subjects during the KLS episodes and when the subjects were not having symptoms. In the laboratory, they measured levels of histamine, hypocretin, and a major metabolite (a substance that is the result of the breakdown) of histamine, called tele-methylhistamine (t-MHA) in the CSF samples.
What Were the Results of the Study?
When tested between KLS episodes, both subjects had normal levels of hypocretin, histamine, and t-MHA. However, when tested during the KLS episode, the hypocretin level of the subject with more severe symptoms decreased to a level typically found in people with Type 1 narcolepsy. The other patient’s hypocretin level decreased by 42% from his level obtained between the KLS episodes, but it did not fall below normal levels. The histamine level of the subject with more severe KLS symptoms dropped twofold when he was having symptoms, as compared with when he was not. The other subject did not have a change in histamine levels when his levels during and between episodes were compared. Neither had a change in t-MHA levels.
What Did The Authors of the Paper Conclude?
Evidence of reversible changes in CSF hypothalamic biomarkers in a typical patient with KLS reinforces the hypothesis that KLS episodes may be caused in some patients by recurrent functional alterations of the hypothalamus. Further longitudinal studies including a larger number of patients are needed to more accurately determine the diagnostic value of measuring CSF hypocretin-1 in KLS patients during acute periods and to assess relationships between abnormal behavior, potential dysautonomia, functional neuroimaging, and CSF hypothalamic biomarkers in and out of symptomatic episodes.
What Does This Mean for People With KLS?
The results of this study indicate that hypocretin levels in the CSF appeared to correlate with KLS episodes in these two patients and may, therefore, serve as a biomarker of KLS. However, additional larger studies are needed to support this finding.
Lopez R, Barateau L, Chenini S, Dauvilliers Y. Preliminary results on CSF biomarkers for hypothalamic dysfunction in Kleine–Levin syndrome. Sleep Med2014; Oct 22. Epub ahead of print.