Sleeping Beauty: Kleine–Levin Syndrome

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.

Keywords: Armodafinil, oxcarbamazepine, postpartum Kleine–Levin syndrome, rapid cycling Kleine–

Levin syndrome

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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:
 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.
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CASE REPORTS
Case 1

Thirty-year old married Muslim male presented with 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.

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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.

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Footnotes

Source of Support: Nil

Conflict of Interest: None declared

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