CASE REPORT
Sleeping Beauty: Kleine–Levin Syndrome Soumiya Mudgal, R. C. Jiloha, Manish Kandpal1, Aparna Das
Departments of Psychiatry, Maulana Azad Medical College and G B Pant Hospital, 1PGIMER and RML Hospital, New Delhi, India
ABSTRACT
Kleine–Levin syndrome (KLS) alias sleeping beauty syndrome, is a rare sleep disorder. Clinically presenting as episodes of hypersomnolence, behavioral and cognitive disturbances, hyperphagia and hypersexuality. KLS may have an idiopathic onset or may be precipitated by neurological event or infection. Until date, no definite underlying cause is established and neither there are any definitive management guidelines. It remains a diagnosis of exclusion after other psychiatric and neurological causes have been ruled out. Coloring of presentation with behavioral and mood elements makes it important for a psychiatrist to be well‑informed about the condition to avoid the erroneous diagnosis. KLS is a devastating illness, which robs the patient of time, experiences, and relationships. An early diagnosis and effective management can help patient escape from the morbidity caused by this disorder. Armodafinil and oxcarbamazepine have found to be effective in two of the case. The emphasis of this report is to add to the existing clinical knowledge of neurologists, psychiatrists and physicians. In the future, research is needed on genetic etiology and management of this disorder. Key words: Armodafinil, oxcarbamazepine, postpartum Kleine–Levin syndrome, rapid cycling Kleine–Levin syndrome
INTRODUCTION Kleine–Levin syndrome (KLS) is a rare disorder with periodic hypersomnia, cognitive and behavioural disturbances. The disease was named, “KLS” by Critchley in 1962 after Willi Kleine and Max Levin who studied multiple cases of hypersomnolence and emphasized the association of periodic somnolence with morbid hunger from 1925 to 1936.[1] International Classification of Sleep Disorders‑3 criteria (2013) states following five key points for diagnosis: A. At least two recurrent episodes of excessive sleepiness of 2 days to several weeks B. Episodes recur at least 1 per 18 months C. Normal alertness, cognitive function, behavior and mood between episodes D. At least one of these during an episode: Address for correspondence: Dr. Soumiya Mudgal, Department of Psychiatry, Maulana Azad Medical College and G B Pant Hospital, New Delhi ‑ 110 002, India. E‑mail: [email protected]
How to cite this article: Mudgal S, Jiloha RC, Kandpal M, Das A. Sleeping Beauty: Kleine-Levin syndrome. Indian J Psychiatry 2014;56:298-300. 298
• Cognitive dysfunction • Altered perception, derealization • Eating disorder (anorexia or hyperphagia) • Disinhibited behavior (such as hypersexuality) E. Symptoms not better explained by other disorders.[2] This disorder because of its sporadic presentation has unknown prevalence. A systematic review of 186 cases showed incidence usually in adolescence with a course lasting for 8 years or more.[3] We describe two cases clinically diagnosed as KLS with atypical presentation and favorable response to armodafinil. CASE REPORTS Case 1 Thirty‑year old married Muslim male presented with Access this article online Quick Response Code Website: www.indianjpsychiatry.org
DOI: 10.4103/0019-5545.140654
Indian Journal of Psychiatry 56(3), Jul‑Sep 2014
Mudgal, et al.: Sleeping beauty - Kleine–Levin syndrome
complaints of excessive sleep episodes of abrupt onset lasting for 14-16 days once a year from last 15 years (onset 15 years age) associated with the irritability, confusion, marked decline in self‑care, demonstration of social responsibilities and regularity at work with no hyperphagia or hypersexuality. Interepisodal periods showed complete recovery. There was no positive past or family history of neurological or psychiatric disorder. History of meningitis, head injury and substance abuse were ruled out. All biochemical, endocrine, radiological parameters and electroencephalography (EEG) were found within normal range. A clinical diagnosis of KLS was made, and patient was put on armodafinil 100 mg oral dose for 10 days. He is maintaining well with no recurrence since last 1 year. Case 2 Twenty‑four year married Muslim female with complaints of episodes of excessive sleep (15-20 days) with anger outburst, irritability with hyperphagia and hypersexuality occurring every month since last 4 years. There was a complicated peripartum and postpartum history in the form of cardiac arrest during emergency caesarean section followed by admission in Intensive Care Unit (ICU) for 15 days. During the stay in ICU and postdischarge there were complaints of auditory hallucinations, confusion, behavioral problems, taking bath 4-5 times a day, disinterest in child care. A diagnosis of postpartum psychosis was made, and she was put on risperidone 4 mg with no response, later on sodium valproate was added, but no major benefits were seen. This presentation continued for 3 months thereafter family noticed remission in complaints of hallucinations but a periodic monthly pattern of excessive sleepiness with feeling of unrealness for surrounding, confusion, irritability, hyperphagia and hypersexuality. There was decreased self‑care and childcare during episodes and during interepisodic periods she maintained well. There was no other significant neurological, psychiatric, past and family history, and these episodes did not have any relation with menstrual cycles. Biochemical and endocrine parameters were within normal range. Magnetic resonance imaging and EEG were found to be normal. Technetium 99m‑ethyl cysteinate dimer brain perfussion study showed hypo perfusion of bilateral frontal lobes. She was tried on various antipsychotic medications, selective serotonin reuptake inhibitor and valproate combinations over 3 years with no response. Periodicity and poor response to medications raised suspicion on the previous line of treatment initially for postpartum psychosis and eventual diagnosis of mood disorder. A clinical diagnosis of KLS was made and armodafinil 100 mg was started, dose was further raised to 300 mg. Later oxcarbamazepine in dose of 600 mg BD was started. Patient reported decreased in duration and more spaced out frequency of episodes of excessive sleep during first 3 months. She is maintaining well on the same treatment and is a symptom free from last 6 months. Indian Journal of Psychiatry 56(3), Jul‑Sep 2014
DISCUSSION Both the cases fulfilled the criteria for Kleine–Levine syndrome, but due to rarity of the disorder they remained undiagnosed for years. While Case 1 is a presentation with idiopathic etiology with no signs of hyperphagia or hypersexuality, Case 2 had onset with or preceded by postpartum psychosis that is not a very common presentation.[4] Also the fact that case reports of KLS in females are very limited, the possibility of KLS was ignored.[3,5] As disease mimics and shares psychiatric conditions in many ways, so a first presentation can be in Psychiatry Outpatient Department as in the case of both our patients. Therefore, it is important to have a high index of suspicion in any case presenting with complaints of episodic hypersomnolence and after ruling out differentials like Kluver–Bucey syndrome, atypical depression, substance abuse and other differentials for hypersolomnelence[2], diagnosis diagnosis of KLS should be made. Lithium, valproate, carbamazepine, amphetamine, L‑dopa, modafinil, armodafinil have been tried for symptomatic treatment and for prevention of relapse with variable results in the absence of definitive treatment.[3,6] In the cases that reported to us the male patient had 1 time treatment and has not got any episode in last 1 year whereas the female patient had a rapid cycling pattern and is continuing medications.[7] Hence, the question arises whether it is advisable to give maintenance treatment to Case 1 or wait for another episode to start a maintenance drug.[5] Kleine–Levin syndrome is a neurological disorder with a lot of psychiatric coloring, therefore, a case can present to neurologist or psychiatrist depending upon patients understanding of symptoms, so it is important for clinicians to have high index of suspicion mainly for atypical presentations to avoid delay in diagnosis or making erroneous diagnosis. Though most cases develop spontaneously but presence of precipitating events should not stop clinician to suspect KLS.[8,9] Armodafinil (100-300 mg) and oxcarbamazepine has been found to be effective in preventing relapse in these two cases of KLS.[10] These case reports aim to highlight that KLS though considered a rare disorder may not be that uncommon and lack of enough available research data is likely to be responsible for missed diagnosis; thus we need more systematic studies regarding etiologies and treatment options. REFERENCES 1. 2. 3.
Pearce JM. Kleine‑Levin syndrome: History and brief review. Eur Neurol 2008;60:212‑4. American Academy of Sleep Medicine. Diagnostic and Coding Manual, International Classification of Sleep Disorders. 3rd ed. Westchester Illinois: American Academy of Sleep Medicine; 2013. 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.
299
Mudgal, et al.: Sleeping beauty - Kleine–Levin syndrome 4. Murthy VS, Kelkar AD, Sonavane SS. Psychosis in a case of kleine‑levin syndrome: A diagnostic challenge. Indian J Psychol Med 2014;36:192‑4. 5. 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. 6. Bansode A, Shah N, Kukreja S, Sonavane S, Desousa A. Klein Levin syndrome - A case report. Indian J Priv Psychiatry 2012;6:52‑4. 7. Gusmao CD, Maski K, Urion D. Kleine‑Levin syndrome with rapid cycling‑case report and review of the literature. Neurology 2014;82:294.
8.
Merriam AE. Kleine‑Levin syndrome following acute viral encephalitis. Biol Psychiatry 1986;21:1301‑4. 9. Will RG, Young JP, Thomas DJ. Kleine‑Levin syndrome: Report of two cases with onset of symptoms precipitated by head trauma. Br J Psychiatry 1988;152:410‑2. 10. Mohapatra S, Sathpathy A, Deo SJ, Rath N. Kleine Levin syndrome and its successful treatment with Armodafinil. German J Psychiatry 2014;17:25‑6.
Source of Support: Nil, Conflict of Interest: None declared
“Quick Response Code” link for full text articles The journal issue has a unique new feature for reaching to the journal’s website without typing a single letter. Each article on its first page has a “Quick Response Code”. Using any mobile or other hand-held device with camera and GPRS/other internet source, one can reach to the full text of that particular article on the journal’s website. Start a QR-code reading software (see list of free applications from http://tinyurl.com/ yzlh2tc) and point the camera to the QR-code printed in the journal. It will automatically take you to the HTML full text of that article. One can also use a desktop or laptop with web camera for similar functionality. See http://tinyurl.com/2bw7fn3 or http://tinyurl.com/3ysr3me for the free applications. 300
Indian Journal of Psychiatry 56(3), Jul‑Sep 2014
Copyright of Indian Journal of Psychiatry is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Sleeping Beauty: Kleine–Levin Syndrome Soumiya Mudgal, R. C. Jiloha, Manish Kandpal1, Aparna Das
Departments of Psychiatry, Maulana Azad Medical College and G B Pant Hospital, 1PGIMER and RML Hospital, New Delhi, India
ABSTRACT
Kleine–Levin syndrome (KLS) alias sleeping beauty syndrome, is a rare sleep disorder. Clinically presenting as episodes of hypersomnolence, behavioral and cognitive disturbances, hyperphagia and hypersexuality. KLS may have an idiopathic onset or may be precipitated by neurological event or infection. Until date, no definite underlying cause is established and neither there are any definitive management guidelines. It remains a diagnosis of exclusion after other psychiatric and neurological causes have been ruled out. Coloring of presentation with behavioral and mood elements makes it important for a psychiatrist to be well‑informed about the condition to avoid the erroneous diagnosis. KLS is a devastating illness, which robs the patient of time, experiences, and relationships. An early diagnosis and effective management can help patient escape from the morbidity caused by this disorder. Armodafinil and oxcarbamazepine have found to be effective in two of the case. The emphasis of this report is to add to the existing clinical knowledge of neurologists, psychiatrists and physicians. In the future, research is needed on genetic etiology and management of this disorder. Key words: Armodafinil, oxcarbamazepine, postpartum Kleine–Levin syndrome, rapid cycling Kleine–Levin syndrome
INTRODUCTION Kleine–Levin syndrome (KLS) is a rare disorder with periodic hypersomnia, cognitive and behavioural disturbances. The disease was named, “KLS” by Critchley in 1962 after Willi Kleine and Max Levin who studied multiple cases of hypersomnolence and emphasized the association of periodic somnolence with morbid hunger from 1925 to 1936.[1] International Classification of Sleep Disorders‑3 criteria (2013) states following five key points for diagnosis: A. At least two recurrent episodes of excessive sleepiness of 2 days to several weeks B. Episodes recur at least 1 per 18 months C. Normal alertness, cognitive function, behavior and mood between episodes D. At least one of these during an episode: Address for correspondence: Dr. Soumiya Mudgal, Department of Psychiatry, Maulana Azad Medical College and G B Pant Hospital, New Delhi ‑ 110 002, India. E‑mail: [email protected]
How to cite this article: Mudgal S, Jiloha RC, Kandpal M, Das A. Sleeping Beauty: Kleine-Levin syndrome. Indian J Psychiatry 2014;56:298-300. 298
• Cognitive dysfunction • Altered perception, derealization • Eating disorder (anorexia or hyperphagia) • Disinhibited behavior (such as hypersexuality) E. Symptoms not better explained by other disorders.[2] This disorder because of its sporadic presentation has unknown prevalence. A systematic review of 186 cases showed incidence usually in adolescence with a course lasting for 8 years or more.[3] We describe two cases clinically diagnosed as KLS with atypical presentation and favorable response to armodafinil. CASE REPORTS Case 1 Thirty‑year old married Muslim male presented with Access this article online Quick Response Code Website: www.indianjpsychiatry.org
DOI: 10.4103/0019-5545.140654
Indian Journal of Psychiatry 56(3), Jul‑Sep 2014
Mudgal, et al.: Sleeping beauty - Kleine–Levin syndrome
complaints of excessive sleep episodes of abrupt onset lasting for 14-16 days once a year from last 15 years (onset 15 years age) associated with the irritability, confusion, marked decline in self‑care, demonstration of social responsibilities and regularity at work with no hyperphagia or hypersexuality. Interepisodal periods showed complete recovery. There was no positive past or family history of neurological or psychiatric disorder. History of meningitis, head injury and substance abuse were ruled out. All biochemical, endocrine, radiological parameters and electroencephalography (EEG) were found within normal range. A clinical diagnosis of KLS was made, and patient was put on armodafinil 100 mg oral dose for 10 days. He is maintaining well with no recurrence since last 1 year. Case 2 Twenty‑four year married Muslim female with complaints of episodes of excessive sleep (15-20 days) with anger outburst, irritability with hyperphagia and hypersexuality occurring every month since last 4 years. There was a complicated peripartum and postpartum history in the form of cardiac arrest during emergency caesarean section followed by admission in Intensive Care Unit (ICU) for 15 days. During the stay in ICU and postdischarge there were complaints of auditory hallucinations, confusion, behavioral problems, taking bath 4-5 times a day, disinterest in child care. A diagnosis of postpartum psychosis was made, and she was put on risperidone 4 mg with no response, later on sodium valproate was added, but no major benefits were seen. This presentation continued for 3 months thereafter family noticed remission in complaints of hallucinations but a periodic monthly pattern of excessive sleepiness with feeling of unrealness for surrounding, confusion, irritability, hyperphagia and hypersexuality. There was decreased self‑care and childcare during episodes and during interepisodic periods she maintained well. There was no other significant neurological, psychiatric, past and family history, and these episodes did not have any relation with menstrual cycles. Biochemical and endocrine parameters were within normal range. Magnetic resonance imaging and EEG were found to be normal. Technetium 99m‑ethyl cysteinate dimer brain perfussion study showed hypo perfusion of bilateral frontal lobes. She was tried on various antipsychotic medications, selective serotonin reuptake inhibitor and valproate combinations over 3 years with no response. Periodicity and poor response to medications raised suspicion on the previous line of treatment initially for postpartum psychosis and eventual diagnosis of mood disorder. A clinical diagnosis of KLS was made and armodafinil 100 mg was started, dose was further raised to 300 mg. Later oxcarbamazepine in dose of 600 mg BD was started. Patient reported decreased in duration and more spaced out frequency of episodes of excessive sleep during first 3 months. She is maintaining well on the same treatment and is a symptom free from last 6 months. Indian Journal of Psychiatry 56(3), Jul‑Sep 2014
DISCUSSION Both the cases fulfilled the criteria for Kleine–Levine syndrome, but due to rarity of the disorder they remained undiagnosed for years. While Case 1 is a presentation with idiopathic etiology with no signs of hyperphagia or hypersexuality, Case 2 had onset with or preceded by postpartum psychosis that is not a very common presentation.[4] Also the fact that case reports of KLS in females are very limited, the possibility of KLS was ignored.[3,5] As disease mimics and shares psychiatric conditions in many ways, so a first presentation can be in Psychiatry Outpatient Department as in the case of both our patients. Therefore, it is important to have a high index of suspicion in any case presenting with complaints of episodic hypersomnolence and after ruling out differentials like Kluver–Bucey syndrome, atypical depression, substance abuse and other differentials for hypersolomnelence[2], diagnosis diagnosis of KLS should be made. Lithium, valproate, carbamazepine, amphetamine, L‑dopa, modafinil, armodafinil have been tried for symptomatic treatment and for prevention of relapse with variable results in the absence of definitive treatment.[3,6] In the cases that reported to us the male patient had 1 time treatment and has not got any episode in last 1 year whereas the female patient had a rapid cycling pattern and is continuing medications.[7] Hence, the question arises whether it is advisable to give maintenance treatment to Case 1 or wait for another episode to start a maintenance drug.[5] Kleine–Levin syndrome is a neurological disorder with a lot of psychiatric coloring, therefore, a case can present to neurologist or psychiatrist depending upon patients understanding of symptoms, so it is important for clinicians to have high index of suspicion mainly for atypical presentations to avoid delay in diagnosis or making erroneous diagnosis. Though most cases develop spontaneously but presence of precipitating events should not stop clinician to suspect KLS.[8,9] Armodafinil (100-300 mg) and oxcarbamazepine has been found to be effective in preventing relapse in these two cases of KLS.[10] These case reports aim to highlight that KLS though considered a rare disorder may not be that uncommon and lack of enough available research data is likely to be responsible for missed diagnosis; thus we need more systematic studies regarding etiologies and treatment options. REFERENCES 1. 2. 3.
Pearce JM. Kleine‑Levin syndrome: History and brief review. Eur Neurol 2008;60:212‑4. American Academy of Sleep Medicine. Diagnostic and Coding Manual, International Classification of Sleep Disorders. 3rd ed. Westchester Illinois: American Academy of Sleep Medicine; 2013. 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.
299
Mudgal, et al.: Sleeping beauty - Kleine–Levin syndrome 4. Murthy VS, Kelkar AD, Sonavane SS. Psychosis in a case of kleine‑levin syndrome: A diagnostic challenge. Indian J Psychol Med 2014;36:192‑4. 5. 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. 6. Bansode A, Shah N, Kukreja S, Sonavane S, Desousa A. Klein Levin syndrome - A case report. Indian J Priv Psychiatry 2012;6:52‑4. 7. Gusmao CD, Maski K, Urion D. Kleine‑Levin syndrome with rapid cycling‑case report and review of the literature. Neurology 2014;82:294.
8.
Merriam AE. Kleine‑Levin syndrome following acute viral encephalitis. Biol Psychiatry 1986;21:1301‑4. 9. Will RG, Young JP, Thomas DJ. Kleine‑Levin syndrome: Report of two cases with onset of symptoms precipitated by head trauma. Br J Psychiatry 1988;152:410‑2. 10. Mohapatra S, Sathpathy A, Deo SJ, Rath N. Kleine Levin syndrome and its successful treatment with Armodafinil. German J Psychiatry 2014;17:25‑6.
Source of Support: Nil, Conflict of Interest: None declared
“Quick Response Code” link for full text articles The journal issue has a unique new feature for reaching to the journal’s website without typing a single letter. Each article on its first page has a “Quick Response Code”. Using any mobile or other hand-held device with camera and GPRS/other internet source, one can reach to the full text of that particular article on the journal’s website. Start a QR-code reading software (see list of free applications from http://tinyurl.com/ yzlh2tc) and point the camera to the QR-code printed in the journal. It will automatically take you to the HTML full text of that article. One can also use a desktop or laptop with web camera for similar functionality. See http://tinyurl.com/2bw7fn3 or http://tinyurl.com/3ysr3me for the free applications. 300
Indian Journal of Psychiatry 56(3), Jul‑Sep 2014
Copyright of Indian Journal of Psychiatry is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
![[Is Sleeping Beauty really asleep?].](/assets/img/hold.png)
