Introduction:

Chances are, you have experienced that dragging, dull semi-conscious

feeling you get from sleep deprivation (lack of sleep), and all you want to do is
take a nap. However, for individuals who are suffering with primary
hypersomnia, they are dealing with this feeling every day. They feel only half-
awake and hardly ever can get enough quality sleep at night to promise them a
refreshed day the next morning. This constant state of being is known as Kleine-
Levin Syndrome or sometimes referred to as Sleeping Beauty Syndrome. The
disease was named, “KLS” by Critchley in 1962 after Willi Kleine and Max Levin
who studied multiple cases of hyper somnolence and emphasized the association
of periodic somnolence with megaphagia to morbid hunger from 1925 to 1936.
One particularly striking form of the disease, Kleine-Levin syndrome, produces
such tiredness and sleep-drunkenness that people are unable to attend school
or work. In males, it can include hypersexual behavior, compulsive
masturbation, a desire for promiscuous sex or making inappropriate sexual
advances, all while in a sleepy, semi-conscious state. Also known as “Sleeping
Beauty Syndrome,” the condition leaves those with the worst cases languishing
in bed in what seems like the opposite of a fairy tale, without a prince’s kiss to
cure them.

Kleine–Levin syndrome (KLS) alias sleeping beauty syndrome, is a rare

neurological or sleep disorder, clinically presenting as episodes of
hypersomnolence, behavioral and cognitive disturbances, hyperphagia and
hypersexuality. 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. Kleine- Levin 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.

Kleine-Levin Syndrome is characterized by recurring periods of excessive

amounts of sleep, altered behavior, and a reduced understanding of the world.
The disorder strikes adolescents primarily but can occur in younger children and
adults. At the onset of an episode the patient becomes progressively drowsy and
sleeps for most of the day and night (hypersomnolence), sometimes waking only
to eat or go to the bathroom. Each episode lasts days, weeks, months or years
during which time all normal daily activities stop. Individuals are not able to care
for themselves or attend school and work. Individuals are not able to attend
school, work or care for themselves. Most are bedridden, tired and
uncommunicative even when awake. In between episodes, those with KLS appear
to be in perfect health with no evidence of behavioral or physical dysfunction.
However they function daily with the frightful reality that they could become sick
again at any moment. KLS episodes may continue to reoccur for a decade or
longer with devastating effects on the adolescent’s life and family. KLS robs
children and young adults of big pieces of their lives, one agonizing episode at a
time.
In addition to excessive sleep, a Kleine-Levin Syndrome (KLS) patient’s
whole demeanor is changed, often appearing “spacey” or childlike. When awake
the patient experiences confusion, disorientation, complete lack of energy
(lethargy), and lack of emotions (apathy). Most patients report that everything
seems out of focus, and that they are hypersensitive to noise and light. In some
cases, food cravings (compulsive hyperphagia) are exhibited. Instances of
uninhibited hyper-sexuality during an episode have also been reported.

Body:
The cause of Kleine-Levin syndrome is unknown, although the disorder
has a strong genetic component. This uncommon sleep disorder tends to run in
families, especially of Jewish ancestry. About 15 percent of the Kleine-Levin
syndrome patients are of Jewish origin and “the incidence reported in Israel is
unproportionately high,” according to a paper in a Jewish medical journal. “The
most promising findings are the familial clustering and a potential Jewish
founder effect, supporting a role for genetic susceptibility factors,” according
to French researchers. This disorder generally appears in adolescence and
subsides on its own. Over time, episodes diminish in frequency and severity,
becoming less disruptive to the individual and family. On average, it takes 8-14
years for patients to “outgrow” Kleine-Levin syndrome, with longer duration in
men, in patients with hypersexuality, and when onset is after age 20.
This condition, although rare, appears to affect adolescent males who are
typically in their teenage years (16 years old). In fact, out of everyone who has
this condition, around 70 percent are male. Women, however, tend to keep the
disorder longer men. Even though there are over 500 reported cases of this
disorder in medical literature, it still often goes under-diagnosed and
unrecognized, which makes it challenging to truly figure out its frequency in
the overall population. More than 500 cases have been reported in the medical
literature. However, because cases of Kleine-Levin syndrome often go
unrecognized, the disorder is under-diagnosed, making it difficult to determine
its true frequency in the general population. In some cases, symptoms subside
with advancing age (spontaneous remission), most often by early adult life.
However, in other cases, the disorder persists throughout adulthood.

Some medications that promote wakefulness can help correct sleep

abnormalities and excessive sleepiness present in Kleine-Levin syndrome.
Amphetamines and lithium have been used successfully in some
patients. Amphetamines helped decrease the oversleeping in 40% of patients.
According to the same review in the journal Brain, “lithium had a higher reported
response rate (41%) for stopping relapses when compared to medical abstention
(19%).”
The treatment for Sleeping Beauty Syndrome or Kleine-Levin Syndrome is
indefinite. Waiting-at-home watchfully is advisable than relying on
pharmacotherapy. Sleepiness can be treated using pills like modafinil,
amphetamines and methylphenidate. This may, however, give rise to other
cognitive symptoms and might develop irritability. The closeness in symptoms
between Kleine-Levin syndrome and other mood disorders have made it
compulsory for the doctors to prescribe carbamazepine and lithium in some
cases for its prevention
The disorder should be distinguished from the periodic reappearance of
sleepiness that is associated with the pre-menstrual cycle in teenagers and can
be controlled using birth-control tablets. The syndrome should also be set aside
from recurrent depression, encephalopathy and psychosis.
Sleeping Beauty Syndrome or Kleine-Levin Syndrome show its appearance
in the adolescents and the symptoms are observed to occur in a range of 2 and
12 times annually. When a single episode occurs, it can last for days or months.
At the end of the episode, the patients lack their ability to recollect the instances.
The symptoms can recur without any warning in the future.
When the health of a patient is diagnosed between the episodes, it shows
normal. There are no registered evidences of physical or behavioral dysfunction.
The patients usually lead a normal life and follow a regular pattern. As he or she
advances into age, the episodes are less frequently observed and may disappear
as well. In some cases, the patients who are in their late fifties have also been
affected by the syndrome. Following is a list of symptoms that are observed in
patients with Sleeping Beauty Syndrome or Kleine-Levin Syndrome:
Hypersomnia or Extreme Sleep: This is a basic symptom of Kleine-Levin
Syndrome and is an essential condition speculated for diagnosis. Patients
usually sleep from 12 to 24 hours and find it difficult to arouse as well.
Uncontrollable Eating (hyperphagia): The patients who are sufferers of Sleeping
Beauty Syndrome or Kleine-Levin Syndrome are often subjected to various
episodes and their occurrence. They often have cravings that are powerful and
show association with junk food or sweets.
Aggressive Sexuality: The sexual urge is profound in some patients leading to
unsuitable sexual advances at times. This hypersexual behavior includes
excessive masturbation, indulgence with multiple partners and bawdy behavior.
Emotional Impairment: Patients are often subjected to diminished
comprehension, memory problems, poor concentration, confusion, and
communication problems. There might also be associated speech impairments
like slurred, childish or monosyllabic speech.
Altered Approach: Most patients often feel disconnected and are often distorted
like living in a dream. Some also experience visual hallucinations or auditory
disturbances as well.
Other Symptoms of Sleeping Beauty Syndrome or Kleine-Levin Syndrome
may include irritability, migraine headaches, hypersensitivity to light and noise
as well as anxiety. Many patients also show certain changes like increased heart
rate or elevated body temperature with symptoms of flu.
Lithium is the only element or drug that has a preventive effect on Sleeping
Beauty Syndrome or Kleine-Levin Syndrome. Studies have shown that the drugs,
which consisted of Lithium helped in preventing the symptom recurrence in most
cases. The curative properties of other mood stabilizers have not yet known and
their effect on the condition has not been determined. Recurrence of Sleeping
Beauty Syndrome or Kleine-Levin Syndrome cannot be prevented with anti-
depressants.

Conclusion:
KLS is a neurological disorder with a lot of psychiatric coloring, therefore, a case
may present to a neurologist, physician, or psychiatrist depending on patients’
awareness, feasibility, and predominant symptoms. Hence, it is important for
clinicians to have high index of suspicion on such atypical presentations. Any
case presenting with episodic hypersomnolence should be evaluated thoroughly
with multidisciplinary approach for timely diagnosis and rational treatment.
Kleine Levin Syndrome (KLS) or Sleeping Beauty Syndrome patient experiences
recurrent episodes of excessive sleep, episodes occur at least once a year, and
are generally 2 days to 4 weeks in duration and during episodes, when awake,
cognition is abnormal with feeling of unreality or confusion. Behavioral
abnormalities such as megaphagia or hypersexuality may occur in some
episodes. The patient has normal alertness, cognitive functioning, and behavior
between the episodes, the condition is not better accounted for by another
mental disorder (e.g, mood disturbance), and is not due to the direct
physiological effects of a substance (e.g., a drug of abuse, a medication) or
another general medical condition (e.g. a metabolic disorder). There is increasing
evidence that the disorder is a genuine disease entity based on its consistent
description in term of clinical presentation, demographics (70% male,
adolescent), evolution (eventually disappears), and therapeutic response (almost
nothing is effective). It may be misdiagnosed as depression or other psychiatric
consequences, with devastating consequences.

References:
1. Pearce JM. Kleine-Levin syndrome: History and brief review. Eur Neurol 2008;60: 212-4.
2. American Academy of Sleep Medicine. Diagnostic and Coding Manual.
International Classification of Sleep Disorders. 3rd ed. Westchester, Illinois:
American Academy of Sleep Medicine; 2013.
3. Minvielle S, et al. Klein-Levin syndrome: a neurological disease with psychiatric
symptoms. Encephale. 2000;26:71-74.
4. Kesler A, et al. Kleine Levin syndrome (KLS) in young females. Sleep.
2000;15:563-37.
5. Will RG, et al. Kleine-Levin syndrome: report of two cases with onset of symptoms
precipitated by head trauma. Br J Psychiatry. 1988;152:410-12.
6. Glaze DG. Kleine-Levin Syndrome. In: NORD Guide to Rare Disorders. Lippincott
Williams & Wilkins. Philadelphia, PA. 2003:544.
7. Dauvilliers Y, et al. Kleine-Levin syndrome: an autoimmune hypothesis based on
clinical and genetic analyses. Neurology. 2002;59:1739-45.
8. Billiard M, Dauvilliers Y. Idiopathic hypersomnia. Sleep Med Rev. 2001;5:349-
358.
9. Pike M, et al. Kleine-Levin syndrome: a case of diagnostic confusion. Arch Disease
Child. 1994;71:355-57.
10. Wurthmann C, et al. Kleine-Levin syndrome. Fortschr Neurol Psychiatr.
1991;59:190-94.
11. Kerkar P., et al. Sleeping Beauty Syndrome. Pain Assist Inc. 14 March 2019.
12. Singh RK, Kaur H, Munjal GC, Malik SC. The Kleine-Levin syndrome: Review and
report of two atypical cases. Indian J Psychiatry. 1990;32:100–5.