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Case Report: Use of Valproate in Kleine Levin Syndrome

Paper Type: Free Essay Subject: Medical
Wordcount: 2662 words Published: 26th Jul 2021

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Successful use of Valproate in Kleine Levin Syndrome: a case report and review of cases reported from India


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.


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 (Yao et al., 2013). Several medications (stimulants, lithium, valproate, antipsychotics, antidepressants) have been reported to provide variable benefit in different symptoms, with lithium being the most widely used drug (Arnulf et al., 2005 & 2012). We are presenting a case of KLS, who had complete remission with valproate and also reviewing the cases reported from India.

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Case details

A 17 year old single male student of 12th 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 four months and he maintained completely well in interepisodic 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 nine months, but started having similar episodes again from mid 2005, due to which Sertraline was 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 hours per day. He was also not responding with these medications, hence differential diagnosis of KLS vs. depression was kept and later finalized to KLS. His heamogram, renal functions, liver functions, blood sugar, routine urine, thyroid functions were within normal limits and chest X ray, ECG, EEG, and MRI 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/liter). On which he has shown significant improvement initially for six month 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 reemergence 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 three years without any episode of hypersomnolence, sexual disinhibition, sadness, or epileptic seizure.


Based on historical reports by Kliene and Levin, KLS was essentially described and termed by Critchley (1962). Thereafter many researchers have reported their cases and reviewed cases with KLS (Arnulf et al., 2005 & 2012). 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 Kliene-levin syndrome, by using PUBMED and Google Scholar, we could find 15 cases reported from India (Aggarwal et al., 2011; Mendhekar et al., 2001; Prabhakaran et al., 1970; Shukla et al., 1982; Sagar et al., 1990; Narayanan et al., 1972; Agrawal & Agrawal, 1979; Malhotra et al., 1997; Gupta et al., 2011). Of them 13 were males and 2 females, similar to male preponderance reported in the literature (Arnulf et al., 2005 & 2012). While presenting to psychiatric services their age was between 9 to 26 years and they had onset between 7 to 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, methyl amphetamine, dextro amphetamine, and modafinil. Longest asymptomatic follow-up period is reported for 2 years (Aggarwal et al., 2011) (as depicted in table-1).

Though literature supported lithium for higher response rate (Arnulf et al., 2005 & 2012), but index patient had remarkable response with Valproate, not with lithium, like earlier two reports (Crumley, 1997; Adlakha & Chokroverty, 2009). Like earlier report (Adlakha & Chokroverty, 2009), index patient also improved on lower dose of Valproate (divalproate 750 mg vs. 500 mg Valproate). Compared to other cases reported from India (Aggarwal et al., 2011; Gupta et al., 2011), 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 (Yao et al., 2013). Valproate may be a good alternative to lithium in terms of efficacy as well as side effect profile.


  1. Yao, C.C., Lin, Y., Liu, H.C., Lee, C.S., 2013. Effects of various drug therapies on Kleine–Levin syndrome: a case report. Gen Hosp Psychiatry. 35, 102.e7-102.e9.
  2. Arnulf, I., Zeitzer, J.M., File, J., Farber, N., Mignot, E., 2005. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain. 128, 2763-76.
  3. Arnulf, I., Rico, T.J., Mignot, E., 2012. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome. Lancet Neurol. 11, 918-28.
  4. Critchley, M., 1962. Periodic hypersomnia and megaphagia in adolescent males. Brain. 85, 627–56.
  5. Aggarwal, A., Garg, A., Jiloha, R.C., 2011. Kleine-Levine syndrome in an adolescent female and response to modafinil. Ann Indian Acad Neurol. 14, 50-2.
  6. Mendhekar, D.N., Jiloha, R.C., Gupta, D., 2001. Kleine-levin syndrome : a report of two cases. Ind J Psychiatry. 43, 276-8.
  7. Prabhakaran, N., Murthy, G.K., Mallya, U.L., 1970. A Case of Kleine-Levin Syndrome in India. Br J Psychiatry. 117, 517-519.
  8. Shukla, G.D., Bajpai, H.S., Mishra, D.N., 1982. Kleine-levin syndrome: a case report from India. Br J Psychiatry. 141, 97-98.
  9. Sagar, R.S., Khandelwal, S.K., Gupta, S., 1990. Interepisodic morbidity in Kleine-Levin syndrome. Br J Psychiatry. 157, 139-141.
  10. Narayanan, H.S., Narayanan Reddy, G.N., Rama Rao, B.S., 1972. A case of Kleine-levine syndrome. Ind J Psychiatry. 14, 356-358.
  11. Agrawal, A.K., Agrawal, A.K., 1979. Kleine-levin syndrome: a case report. Ind J Psychiatry. 21, 286-287.
  12. Malhotra, S.M., Das, M.K., Gupta, N., Muralidharan, R, 1997. A Clinical Study of Kleine-levin syndrome evidence for hypothalamic-pituitary axis dysfunction. Biol Psychaitry. 42, 299-301.
  13. Gupta, R., Lahan, V., Srivastava, M., 2011. Kleine-Levin syndrome and idiopathic hypersomnia: Spectrum disorders. Ind J Psychol Med. 33, 194-8.
  14. Crumley, F.E., 1997. Valproic acid for Kleine-Levin syndrome. J Am Acad Child Adolesc Psychiatry. 36, 868-9.
  15. Adlakha, A., Chokroverty, S., 2009. An adult onset patient with Kleine-Levin syndrome responding to valproate. Sleep Med. 10, 391-3.

Table-1: Reported cases with Kleine Levin syndrome from India



Presentation (other than hypersomnolence)

Treatment & outcome

Mendhekar et al, 2001

11 year male

13 year male

Onset at 11 year & 13 year; preceded with fever; symptoms- headache, confusion, odd behavior

2nd case-sexual disinhibition; EEG, CT head- normal

Complete remission with Lithium

Malhotra et al, 1997

14 years female

16 years male

13 years male

17 year male

Onset at 12 years (case-1), 15 years (case-2), 11 years (case-3), 16.5 years (case-4) of age

Symptoms-Hyperphagia, social & sexual disinhibition

Duration of episodes: 3-4 days (case-1), 10 days (case-2), 2-4 weeks (case-3), 3-4 days (case-4)

Preceded by fever in cases 2 and 3

EEG (case-1): right temporoparieto-occipital sharp wave

Cases-1 & 2 remitted spontaneously after five and two episodes, respectively

Case-3 was given lithium carbonate 450 mg/day & remained well at 18 months follow-up

Case-4 lithium was tried but stopped due to side effects. Asymptomatic for 9 months follow-up

Sagar et al, 1990

16 year male

16 year male

18 year male

Onset at 10 years (case-1), 12 years (case-2), 17 years (case-3) of age; Preceded by fever in cases 1 & 3

Symptoms- Hyperphagia, social & sexual disinhibition, academic decline

Duration of episodes: 2-3 weeks (case-1), 8-9 days (case-2), 7-10 days (case-3)

Inter episodic IQ 90 (case-1), 80 (case-2), 71 (case-3)

Carbamazepine tried in case-2, but stopped due to lack of efficacy

Rest cases improved without any medication

Prabhakaran et al, 1970

26 year male

Preceded by fever

Hyperphagia, sexual disinhibition, poor memory

Duration of episode: 3-4 days, Inter episodic IQ=75

He maintained well up to 6 months of follow-up without medications.

Narayanan et al, 1972

21 year male

Onset 19 year; had hyperphagia

Duration of episode: 3-4 days

Methylamphetamine 30 mg was given upon which he improved

Agarwal & Agarwal, 1979

16 year male

Onset at 16 year; Preceded by fever

Symptoms- hyperphagia, visual hallucination

Duration of episode 6-10 weeks, Inter episodic IQ=75

Earlier misdiagnosed with schizophrenia and tried on phenothiazine.

Complete remission on Dextroamphetamine

Gupta et al, 2011

9 year male

Onset at 7 year. Duration of episode: 1 year

Symptoms- hyperphagia, weight gain

IQ=75 (composite score), MRI brain- normal

Treatment and follow-up not mentioned

Aggawal et al, 2011

22 year female

Onset at 16 year; preceded by fever

Symptoms- hyperphagia, confusion, irrelevant talk, sexual disinhibition. Duration of episode: 15-20 days

On Methylamphetamine 25 mg- asymptomatic for 1 year and on Modafinil 100 mg- asymptomatic for 2 year.

Shukla et al, 1982

25 year male

Onset at 24 year; preceded by fever

Symptoms- hyperphagia, oddities, irrelevant talk, sexual disinhibition. Duration of episode: 10 days

Had three episodes before prescribing Dexedrine 5 mg. later maintained well up to 5 months of follow-up.


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