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Year : 2015  |  Volume : 37  |  Issue : 3  |  Page : 352-354  

Successful use of valproate in Kleine-Levin syndrome: A case report and review of cases reported from India

1 Department of Psychiatry, All India Institute of Medical Science, Jodhpur, Rajasthan, India
2 Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication17-Aug-2015

Correspondence Address:
Naresh Nebhinani
Department of Psychiatry, All India Institute of Medical Science, Jodhpur - 342 005, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7176.162931

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Kleine-Levin syndrome (KLS) is characterized by recurrent episodes of hypersomnia and other symptoms and it is a really challenging for the physician, since its causes are not yet clear, and available treatment options are not having adequate support. Here, we are reporting a case with successful use of valproate in KLS and also reviewing the cases reported from India.

Keywords: India, Kleine-Levin syndrome, valproate

How to cite this article:
Nebhinani N, Avasthi A, Modi M. Successful use of valproate in Kleine-Levin syndrome: A case report and review of cases reported from India. Indian J Psychol Med 2015;37:352-4

How to cite this URL:
Nebhinani N, Avasthi A, Modi M. Successful use of valproate in Kleine-Levin syndrome: A case report and review of cases reported from India. Indian J Psychol Med [serial online] 2015 [cited 2020 May 29];37:352-4. Available from:

   Introduction Top

Kleine-Levin syndrome (KLS) is a rare disorder which mainly affects adolescent boys and characterized by recurrent episodes of hypersomnia, and sometime along with hyperphagia, behavioral and cognitive disturbances, and hypersexuality. [1] Several medications (stimulants, lithium, valproate, antipsychotics, and antidepressants) have been reported to provide variable benefit in different symptoms, with lithium being the most widely used drug. [2],[3] We are presenting a case of KLS, who had complete remission with valproate and also reviewing the cases reported from India.

   Case Report Top

A 17-year-old single male student of 12 th standard, presented to our psychiatric outpatient clinic in September 2004 with hypersomnolence, low mood, decreased appetite and interest in studies, social and sexual disinhibition (such as singing obscene songs loudly at home, and touching unconsenting females' including mother's body parts-limbs, face and genitalia). Onset was acute, without any elicitable precipitating factor and course was episodic with average 7-10 days episode in every month for last 4 months and he maintained completely well in inter episodic period.

Provisional diagnosis of recurrent depressive disorder (brief episodes) was kept and he was started on sertraline (50 mg), on which he responded well. He remained asymptomatic for nearly 9 months, but started having similar episodes again from mid-2005, due to which sertraline were gradually hiked up to 150 mg/day, but of no use. Hence, he was admitted in our inpatient setting in March, 2006 for diagnostic evaluation and further management. After detailed evaluation, it was found that his sadness was not pervasive and depressive cognitions and associated disturbances were not present and hypersomnia remained predominant complaint as initially, he was sleeping 16-20 h/day. He was also not responding with these medications, hence differential diagnosis of KLS versus depression was kept and later finalized to KLS. His hemogram, renal functions, liver functions, blood sugar, routine urine, thyroid functions were within normal limits and chest X-ray, electrocardiography, electroencephalography (EEG), and magnetic resonance imaging brain were normal. In view of good literature support lithium was started from 600 mg/day and hiked to 900 mg/day (serum level 0.8 mEq/L). On which he has shown significant improvement initially for 6 months, but later again started experiencing similar symptoms. He also had three episodes of fall, unresponsiveness and epileptiform discharge in EEG twice. Hence, in view of seizure disorder and lack of response, neurologist's consultation was sought, who opined to start antiepileptic medication. Hence, lithium was switched to valproate (750 mg/day) in December 2006, on which he maintained completely well for 4 years, except brief re-emergence of symptoms on discontinuing valproate, which improved completely on resuming the medication. Valproate was gradually tapered and stopped in January 2011 on insistence of patient and family with discussing its pros and cons. Now index case has been maintaining well-off valproate for last 3 years without any episode of hypersomnolence, sexual disinhibition, sadness, or epileptic seizure.

   Discussion Top

Based on historical reports by Kliene and Levin, KLS was essentially described and termed by Critchley. [4] Thereafter, many researchers have reported their cases and reviewed cases with KLS. [2],[3] Here, we are reporting a case with KLS, who responded well with valproate, after diagnostic dilemma and different psychotropic medications and also reviewing the other cases reported from India.

In our electronic search for Indian studies on KLS, by using PubMed and Google Scholar, we could find 15 cases reported from India. [5],[6],[7],[8],[9],[10],[11],[12],[13] Of them 13 were males and 2 females, similar to male preponderance reported in the literature. [2],[3] While presenting to psychiatric services their age was between 9 and 26 years and they had onset between 7 and 24 years of age. In two-third of patients (10 out of 15 patients), it was preceded with fever and their episodes of somnolence were lasted from 3 days to 10 weeks. Hypersomnia and hyperphagia were present in all, while two-third of patients also had social and sexual disinhibition (11 out of 15 patients). Other symptoms were cognitive disturbances (low intelligence quotient, impaired memory, confusion, and academic decline), irrelevant talk, and perceptual disturbances. Nearly one-third of patients improved spontaneously without any medication, while rest was given lithium, carbamazepine, methylamphetamine, dextroamphetamine, and modafinil. Longest asymptomatic follow-up period is reported for 2 years [Table 1]. [5]
Table 1: Reported cases with KLS from India

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Though literature supported lithium for higher response rate, [2],[3] but index patient had remarkable response with valproate, not with lithium, like earlier two reports. Like earlier report, [14],[15] index patient also improved on lower dose of valproate (divalproate 750 mg vs. 500 mg valproate). Compared to other cases reported from India, [5],[13] index patient had longest follow-up (7 years) and remained asymptomatic in this period, except small exacerbation on discontinuation of valproate treatment, which improved completely on resuming the drug. Similar to our patient, anticonvulsants (like valproate) are the preferred treatment for KLS patient, and may also offer benefits in case of comorbid epilepsy. [1] Valproate may be a good alternative to lithium in terms of efficacy as well as side-effect profile.

   References Top

Yao CC, Lin Y, Liu HC, Lee CS. Effects of various drug therapies on Kleine-Levin syndrome: a case report. Gen Hosp Psychiatry 2013;35:102.e7-9.  Back to cited text no. 1
Arnulf I, Zeitzer JM, File J, Farber N, Mignot E. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain 2005;128:2763-76.  Back to cited text no. 2
Arnulf I, Rico TJ, Mignot E. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome. Lancet Neurol 2012;11:918-28.  Back to cited text no. 3
Critchley M. Periodic hypersomnia and megaphagia in adolescent males. Brain 1962;85:627-56.  Back to cited text no. 4
Aggarwal A, Garg A, Jiloha RC. Kleine-Levine syndrome in an adolescent female and response to modafinil. Ann Indian Acad Neurol 2011;14:50-2.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
Mendhekar DN, Jiloha RC, Gupta D. Kleine-levin syndrome: a report of two cases. Indian J Psychiatry 2001;43:276-8.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
Prabhakaran N, Murthy GK, Mallya UL. A case of Kleine-Levin syndrome in India. Br J Psychiatry 1970;117:517-9.  Back to cited text no. 7
Shukla GD, Bajpai HS, Mishra DN. Kleine-levin syndrome: a case report from India. Br J Psychiatry 1982;141:97-8.  Back to cited text no. 8
Sagar RS, Khandelwal SK, Gupta S. Interepisodic morbidity in Kleine-Levin syndrome. Br J Psychiatry 1990;157:139-41.  Back to cited text no. 9
Narayanan HS, Narayanan Reddy GN, Rama Rao BS. A case of Kleine-levine syndrome. Indian J Psychiatry 1972;14:356-8.  Back to cited text no. 10
  Medknow Journal  
Agrawal AK, Agrawal AK. Kleine-levin syndrome: a case report. Indian J Psychiatry 1979;21:286-7.  Back to cited text no. 11
Malhotra S, Das MK, Gupta N, Muralidharan R. A clinical study of Kleine-Levin syndrome with evidence for hypothalamic-pituitary axis dysfunction. Biol Psychiatry 1997;42:299-301.  Back to cited text no. 12
Gupta R, Lahan V, Srivastava M. Kleine-levin syndrome and idiopathic hypersomnia: spectrum disorders. Indian J Psychol Med 2011;33:194-8.  Back to cited text no. 13
[PUBMED]  Medknow Journal  
Crumley FE. Valproic acid for Kleine-Levin syndrome. J Am Acad Child Adolesc Psychiatry 1997;36:868-9.  Back to cited text no. 14
Adlakha A, Chokroverty S. An adult onset patient with Kleine-Levin syndrome responding to valproate. Sleep Med 2009;10:391-3.  Back to cited text no. 15


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