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Kleine-Levin Syndrome and Response to Modafinil in a Young Woman
Ashish Aggarwal; Amit Garg; Rc Jiloha
The Journal of Neuropsychiatry and Clinical Neurosciences 2011;23:E33-E34.
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Department of Psychiatry, Indira Gandhi Medical College, Shimla, India

Department of Psychiatry, GB Pant Hospital, New Delhi, India

To the Editor: Kleine-Levin syndrome is described as a triad of recurrent hypersomnolence, hyperphagia, and hypersexuality (1). However, an incomplete presentation characterized by hypersomnia (which is mandatory for clinical diagnosis), with or without hyperphagia, hypersexuality, cognitive disturbances, mood symptoms, compulsive behaviors, and perceptual abnormalities has also been described (2). Kleine-Levin syndrome, though more common in males, has been reported to occur in females as well (3). Treatment options for management of Kleine-Levin syndrome have generally met with limited success, although lithium has been reported to prevent relapses (4). Other medications that have been used include antidepressants, antipsychotics, benzodiazepines, amphetamines, and even ECT. We report the case of a young woman with Kleine-Levin syndrome and her favorable response to modafinil.

A 22-year-old woman presented with an episodic illness of excessive sleep for past 6.5 years. She had an uneventful birth and developmental history and did not have past or family history of psychiatric or neurological illness. The first episode started after a viral fever at 15 years old. A week after the fever subsided, the first episode started abruptly with complaints of increased sleep, confusion, dream-like state, and irritability with intermittent irrelevant talks. She started sleeping more than her routine sleep. She would sleep for 16–18 hours in a day and would wake up for eating and elimination. Sometimes she had to be awakened to have her meals. She could be aroused without difficulty but would prefer to go right back to sleep, would be irritable, and would not like to talk to anyone. The patient also complained that the things and the people around her did not appear real to her, and she would touch things to establish the reality. Her self-care also decreased and she was forced to take baths and change clothes. She also became fearful and would ask her mother to sleep with her, but the duration and quality of night time sleep was adequate. This was not present in her premorbid state.

The patient stopped going to the school. Her menstrual history revealed irregular cycles and oligomenorrhea, but this episode was not related to her menstrual period. A diagnosis of postviral depression was made and the patient was treated with multivitamins. This episode lasted for 13 days and there was complete spontaneous recovery. The patient had complete memory of the episode. In the next episode, 8 months later, a diagnosis of recurrent depressive disorder was made and the patient was treated with sertraline, 100 mg/day. In the next 2 years, she had three more episodes (8 and 3 months apart) each lasting approximately 25 days, which occurred despite treatment with sertraline. In the fifth episode, she was admitted and we made a diagnosis of periodic hypersomnia. She was treated with methylphenidate, up to 35 mg/day. This episode lasted for 35 days. During OPD follow up fluoxetine was added, up to 40 mg/day. She remained symptom free for the next 2 years and did not follow-up.

In the following year, our patient had three similar episodes (7 and 2 months apart) each being precipitated by sleep deprivation and lasting for approximately 15–20 days. She was admitted during the eighth episode and a diagnosis of recurrent hypersomnia was made. We began treatment with methylphenidate, which was gradually increased to 25 mg/day. Her gynecological referral and investigations, including serum prolactin, luteinizing hormone, follicle-stimulating hormone, and thyroid function tests, were normal. Routine investigations, including CBC, fasting blood glucose, kidney function test, urine R/M, and liver function tests were normal. Her abdomen ultra sonogram, a brain MRI, and EEG were normal. This episode aborted in 12 days and she was continued on same treatment. Following this, she was symptom free for 21 months though she took treatment for 1 year only.

The patient presented to us on day 3 of ninth episode with similar symptoms. Outside the hypersomnia periods, she was asymptomatic. She did not cooperate for a polysomnographic test and thus it could not be done. We made a diagnosis of Kleine-Levin syndrome and she began treatment with modafinil, 100 mg/day increased to 200 mg/day on third day. She showed improvement in her symptoms from the fourth day after starting treatment and was subsequently discharged. She has been symptom-free, taking 100 mg of modafinil for 2 years of regular follow up.

In 1898, a syndrome characterized by periodic hypersomnia and morbid hunger was described, but it was not until 1925 that a complete clinical delineation was made by a German psychiatrist Willi Kleine in his report on five boys. Additional affected males were described by Max Levin in 1929 and later in 1936. Critchley and Hoffman, who coined the term Kleine-Levin syndrome in 1942, were the first to suggest that the syndrome exclusively affected adolescent boys. Later on, females with Kleine-Levin syndrome were also reported.3 The common knowledge that females are the exception to this diagnosis can explain the delay in the diagnosis of girls presenting with features of Kleine-Levin syndrome.

The diagnosis of Kleine-Levin syndrome is based on clinical features alone, as there are no specific laboratory tests that can help in establishing the diagnosis of Kleine-Levin syndrome.5 Impairment of cognitive functions and a wide variety of behavioral abnormalities are commonly associated.6

Our patient presented with episodic course and spontaneous remission of each episode and normalcy in between the episodes. Characteristic features of each episode were hypersomnia, eating excessively, disinhibited behavior, affective features like irritability, social withdrawal, cognitive disturbance, and lack of personal care. The patient experienced onset after a high-grade fever and also displayed features of sexual disinhibition, confusion, dream-like state, and intermittent irrelevant talks—important features of Kleine-Levin syndrome.

Limited literature is available on the management of Kleine-Levin syndrome. Lithium had been reported to be useful but is associated with long-term problems of regular serum monitoring, side effects in females, and problems with pregnancy. Another option is using stimulants like methylphenidate. With increasing awareness among patients and also difficulty in procuring methylphenidate, there is a need for consideration of other treatment options for patients with Kleine-Levin syndrome. Our cases responded very well to modafinil. Previous reported use of modafinil has revealed inconsistent results.1,7

Our report suggests that modafinil could be used in treating Kleine-Levin syndrome. More systemic research is warranted to study the long-term effects of this drug on the course of Kleine-Levin syndrome.

Arnulf  I;  Zeitzer  JM;  File  J:  Kleine-levin syndrome: a systematic review of 186 cases in the literature.  Brain 2005; 128:2763–2776
[PubMed]
[CrossRef]
 
Sheldon  SH:  Kleine-Levin syndrome and recurrent hypersomnias, in  Principles and Practice of Pediatric Sleep Medicine , 1st ed. Sheldon  SH;  Ferber  R;  Kryger  MH.  Philadelphia,  Elsevier Health Sciences, 2005
 
Duffy  JP;  Davison  K:  A female case of the Kleine-Levin syndrome.  Br J Psychiatry 1968; 114:77–84
[PubMed]
[CrossRef]
 
Filippo  M;  Bertini  N;  Gabriele  MI:  Efficacy of lithium treatment in Kleine-Levin syndrome.  Eur Psychiatry 2002; 17:232–233
[PubMed]
[CrossRef]
 
Gallinek  A:  Syndromes of episodic hypersomnia, bulimia, and abnormal mental states.  JAMA 1954; 154:1081–1083
[CrossRef]
 
Pike  M;  Stores  G:  Kleine-Levin syndrome: a cause of diagnostic confusion.  Arch Dis Child 1994; 71:355–357
[PubMed]
[CrossRef]
 
Chakraborty  R;  Chatterjee  A:  Comorbid obsessive-compulsive disorder in a patient with Kleine-Levin syndrome.  German Journal of Psychiatry 2007; 10:1–2
 
References Container
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References

Arnulf  I;  Zeitzer  JM;  File  J:  Kleine-levin syndrome: a systematic review of 186 cases in the literature.  Brain 2005; 128:2763–2776
[PubMed]
[CrossRef]
 
Sheldon  SH:  Kleine-Levin syndrome and recurrent hypersomnias, in  Principles and Practice of Pediatric Sleep Medicine , 1st ed. Sheldon  SH;  Ferber  R;  Kryger  MH.  Philadelphia,  Elsevier Health Sciences, 2005
 
Duffy  JP;  Davison  K:  A female case of the Kleine-Levin syndrome.  Br J Psychiatry 1968; 114:77–84
[PubMed]
[CrossRef]
 
Filippo  M;  Bertini  N;  Gabriele  MI:  Efficacy of lithium treatment in Kleine-Levin syndrome.  Eur Psychiatry 2002; 17:232–233
[PubMed]
[CrossRef]
 
Gallinek  A:  Syndromes of episodic hypersomnia, bulimia, and abnormal mental states.  JAMA 1954; 154:1081–1083
[CrossRef]
 
Pike  M;  Stores  G:  Kleine-Levin syndrome: a cause of diagnostic confusion.  Arch Dis Child 1994; 71:355–357
[PubMed]
[CrossRef]
 
Chakraborty  R;  Chatterjee  A:  Comorbid obsessive-compulsive disorder in a patient with Kleine-Levin syndrome.  German Journal of Psychiatry 2007; 10:1–2
 
References Container
+
+

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PubMed Articles
[Kleine-Levin syndrome: state of the art]. Rev Neurol (Paris) 2008 Aug-Sep;164(8-9):658-68.
Kleine-Levin syndrome and response to modafinil in a young woman. J Neuropsychiatry Clin Neurosci 2011;23(1):E33-4.