Kleine Levin syndrome

Posted by barsta @barsta, Dec 6, 2011

My son has been diagnosed and is undergoing additional testing prior to treatment. It started about 1-2 years ago right about puberty. He is currently 14 years old and continues to get worse.

Any thoughts on treatment of getting the trigger in the brain to help in getting him awake in the mornings?

We have tried multiple things, smelling salts, nicotine patches….


Welcome to Connect, @davidwhitehurstbrown. Thank you for posting the references. Do you or a family member have Kleine-Levin syndrome?

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Thanks for your note of welcome. Kleine-Levin syndrome does not affect me or a close family member. In my 1993 publication “Abnormal fluctuations of acetylcholine and serotonin” (Medical Hypotheses vol. 40, pp. 309–310, I speculated that prolonged low levels of acetylcholine within the mammalian brain might be correlated with KLS symptoms. My speculations might be relevant to the Crick-Mitchison theory of REM sleep.


Abnormal regulation of leptin, orexin, and/or ghrelin might cause, or be correlated with, some of the symptoms of Kleine-Levin syndrome (KLS). Injections of the orexin-1 receptor antagonist SB-334867 might be a plausible therapy for KLS.
http://press.endocrine.org/doi/abs/10.1210/jc.2004-1003 Spiegel, K., Leproult, R., L’Hermite-Balériaux, M., Copinschi, G., Penev, P. D., & Van Cauter, E. (2004). Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. The Journal of clinical endocrinology & metabolism, 89(11), 5762-5771.


Acetylcholinesterase inhibitors (such as tacrine) might be a plausible experimental therapy for some cases of KLS.
NMDA receptor antagonists (such as memantine) might be a plausible experimental therapy for some cases of KLS.
http://neuro.psychiatryonline.org/doi/full/10.1176/appi.neuropsych.13050110 U. K. Rout, M. S. Michener, & D. M. Dhossche. “GAD65 Autoantibodies in Kleine-Levin Syndrome.” The Journal of neuropsychiatry and clinical neurosciences 26, no. 2 (2014): E49-E51.
http://www.neurology.org/content/59/11/1739.short Y. G. Dauvilliers, Y., G. Mayer, et al. “Kleine-Levin syndrome An autoimmune hypothesis based on clinical and genetic analyses.” Neurology 59, no. 11 (2002): 1739-1745.
“Testosterone is a vasoactive hormone that predominantly has vasodilatory actions on several vascular beds, although some studies have reported conflicting effects.”
http://joe.endocrinology-journals.org/content/217/3/R47.short D. M. Kelly & T. H. Jones. “Testosterone: a vascular hormone in health and disease.” Journal of Endocrinology 217, no. 3 (2013): R47-R71.
If some cases of KLS result from an autoimmune disease, then the damage induced by autoantibodies crossing the blood-brain barrier might increase in adolescence because of the vasodilation caused by testosterone.


According to a 2015 KLS review by Arnulf (presenting evidence published by Laval, Ann Neurology, 2015):
“Lithium therapy
• Complete responders: 36.6% 
 • Partial responders: 51% 
 • Non responders: 12.4% 
 • 9.8% had « mini-episodes » (1 day) on lithium 
 • 13 patients had an episode after stopping lithium 2 consecutive nights 
 • Level IV evidence of benefit in KLS 
 • Lithium : 1 month less in episode per year 
 • The level should be high and monitored”
According to a 2014 KLS review by Miglis and Guilleminault:
“… Although an autoimmune mechanism has been suggested, there are likely heterogeneous factors at play in certain susceptible individuals. When combined with a precipitating event such as a minor infection, a transient multifocal encephalopathy ensues. It has been proposed that such a precipitating event may lead to transient permeability of the blood–brain barrier, thus predisposing these individuals to recurrent events. An animal model would add much to the understanding of the underlying pathophysiology. This is yet to be developed and should be considered in future research. …”
In Table 4 on page 2771 there is a list of attempted treatments for KLS:
http://brain.oxfordjournals.org/content/128/12/2763.full I. Arnulf, J. M. Zeitzer, et al. “Kleine–Levin syndrome: a systematic review of 186 cases in the literature.” Brain 128, no. 12 (2005): 2763-2776.

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