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{{Infobox_Disease |
== Historical Perspective: ==
  Name          = {{PAGENAME}} |
KLS was first introduced by Willi Kleine in 1925 as a " periodic sleep disorder," focusing on the
  Image          = |
recurrent hypersomnia and hyperphagia. In 1936, Max Levin expanded the description by
  Caption        = |
including the excessive hunger characteristic of the syndrome. The name "Kleine-Levin Syndrome" was proposed by Critchley and Hoffman in 1942, based on their observations, which included cases among naval personnel serving during World War II. Critchley provided a more precise definition of the syndrome, refining the diagnosis with his observations and contributing to a clearer understanding of the condition and proposed Kleine-Levin Syndrome as an official
  DiseasesDB    = 29520 |
name of the disease.<ref name="pmidPMID: 26739970">{{cite journal| author=Al Suwayri SM| title=Kleine-Levin syndrome. Familial cases and comparison with sporadic cases. | journal=Saudi Med J | year= 2016 | volume= 37 | issue= 1 | pages= 21-8 | pmid=PMID: 26739970 | doi=10.15537/smj.2016.1.12992 | pmc=4724674 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26739970  }} </ref>
  ICD10          = {{ICD10|G|47|8|g|40}} |
  ICD9          = {{ICD9|327.13}} |
  ICDO          = |
  OMIM          = 148840 |
  MedlinePlus    = |
  eMedicineSubj  = |
  eMedicineTopic = |
  MeshID        = D017593 |
}}
{{SI}}
{{CMG}}


==Overview==
== Pathophysiology: ==
'''Kleine-Levin Syndrome''', or KLS, is an extremely rare disorder characterized by the need for excessive amounts of sleep ([[hypersomnia]]), (e.g. up to 20 hours a day); excessive food intake (compulsive [[hyperphagia]]); and an [[hypersexuality|abnormally uninhibited sexual drive]]. Adolescent males and females are the predominant victims of the disorder. There are only about 500 known sufferers of this condition in the world. However, because KLS is sporadic in its appearances, some doctors believe that this number is, in reality, much higher and the reason that it is not publicly noted is because this disease is extremely difficult to diagnose.<ref> J. M. S. Pearce. Kleine-Levin Syndrome: History and Brief Review. Eur Neurol, 2008, 60: 212-214.</ref>
In KLS, active symptoms are linked to decreased activity in the thalamus of the brain, which contributes to excessive sleep. This decrease in thalamic activity is also linked to other symptoms such as emotional blunting, increased sexual behavior, and a sense of detachment from reality. Patients who experience the disease onset more recently or have had more episodes in the past year often show reduced brain metabolism in the [[hippocampus]] and posterior brain regions.However, about half of the patients exhibit increased metabolic activity in the frontal areas of the brain. These changes in brain function not only explain the [[hypersomnia]] but also account for the behavioral and cognitive symptoms associated with the condition.


==Presentation==
== Symptoms: ==
Individual sufferers may often become irritable, lethargic, and/or apathetic. KLS patients may appear disoriented and report [[hallucination]]s. Symptoms are [[cyclical]]; with days to weeks (even up to months) of suffering interspersed by weeks or months (even up to years) symptom-free. Although resolution of the disorder may occur for some in later life, this is not universal.
The main feature of the disease is recurrent extreme sleepiness and during the episodes, they
also experience, confusion, change in mood, behavior alteration, and feeling like things aren&#39;t real overeating symptoms vary from person to person.<ref name="pmidPMID: 28778233">{{cite journal| author=Al Suwayri SM, BaHammam AS| title=The "Known Unknowns" of Kleine-Levin Syndrome: A Review and Future Prospects. | journal=Sleep Med Clin | year= 2017 | volume= 12 | issue= 3 | pages= 345-358 | pmid=PMID: 28778233 | doi=10.1016/j.jsmc.2017.03.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28778233  }} </ref>


==Causes==
== Causes: ==
While some researchers speculate that there may be a hereditary predisposition, others believe the condition may be the result of an [[autoimmune disorder]].<ref>[http://med.stanford.edu/school/Psychiatry/narcolepsy/KLS.html Kleine-Levin Syndrome - Center for Narcolepsy - Stanford University School of Medicine<!-- Bot generated title -->]</ref> Both proposals need not be mutually exclusive with the result being a malfunction of the portion of the brain that helps to regulate functions such as sleep, appetite, and body temperature ([[hypothalamus]]).<ref> R. Poryazova, B. Schnepf, P. Boesiger, C. L. Bassetti. Magnetic resonance spectroscopy in a patient with Kleine-Levin syndrome. J Neurol, 2007, Oct, 254(10): 1445-6.</ref>  Recent studies also suggest that there may be a link to a deficiency of dopamine transporter density in the lower striatum.<ref> M. Q. Hoexter, M. C. Shih, D. D. Mendes, C. Godeiro-Junior, A. C. Felicio, Y. K. Fu, S. Tufik, R. A. Bressan. Lower dopamine transporter density in an asymptomatic patient with Kleine-Levin syndrome. Acta Neurol Scand, 2008, May, 117(5): 370-3.</ref>
The cause of the diseases is still unknown but some factors are still considered as the potential
causes of the diseases such as genetic factors, infectious or immune-mediated causes,neuropathological Causes and other factors.<ref name="pmidPMID: 29532411">{{cite journal| author=AlShareef SM, Smith RM, BaHammam AS| title=Kleine-Levin syndrome: clues to aetiology. | journal=Sleep Breath | year= 2018 | volume= 22 | issue= 3 | pages= 613-623 | pmid=PMID: 29532411 | doi=10.1007/s11325-017-1617-z | pmc=6133116 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29532411  }} </ref>


== Demographics ==
=== Genetic factor: ===
A 2008 study of 108 KLS patients found that the majority of cases were present in adolescent males, with a mean sex ratio of 3:1.  The average age of onset was 15.7 years, with 81.7% experiencing their first episode between 10 and 20 years of age.  Age ranged from 6 to 59 years when patients experienced their first episode.  Females tended to be slightly older than males at first onset, even though they tended to experience puberty earlier. In the US population, KLS presents in Caucasians with three times the expected frequency, and with six times the expected frequency in those of Jewish heritage.<ref> I. Arnulf, L. Lin, N. Gadoth, J. File, M. Lecendreux, P. Franco, J. Zeitzer, B. Lo, J. H. Faraco, E. Mignot. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol, 2008 Apr; 63(4): 482-93.</ref>
The specific gene causing the KLS has not been identified yet but some literature suggests that genetics might be involved in the development of the diseases. There are many cases of KLS among Ashkenazi Jews and it often runs in families including (identical twins), the family members of Patients with KLS have a higher chance of developing conditions themselves. Indicating a possible genetic link. Reported literature suggested the [[TRANK1]] gene which controls the body's internal clock and is also associated with [[bipolar]] and [[schizophrenia]]<ref name="pmidPMID: 33737391">{{cite journal| author=Ambati A, Hillary R, Leu-Semenescu S, Ollila HM, Lin L, During EH | display-authors=etal| title=Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci. | journal=Proc Natl Acad Sci U S A | year= 2021 | volume= 118 | issue= 12 | pages=  | pmid=PMID: 33737391 | doi=10.1073/pnas.2005753118 | pmc=7999876 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33737391  }} </ref>  


== First Onset ==
=== Infectious or immune-mediated cause: ===
About 90% of KLS patients associate an event with their first KLS episode. This event is most often a type of infection or cold, but may also be associated with stress, sleep deprivation, alcohol or marijuana use, physical exertion, traveling, or head trauma. This causes some to think that there may be some immunological link, but so far there is no clear proof of this.  Only a quarter of KLS patients report events triggering subsequent episodes.<ref> I. Arnulf, L. Lin, N. Gadoth, J. File, M. Lecendreux, P. Franco, J. Zeitzer, B. Lo, J. H. Faraco, E. Mignot. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol, 2008 Apr; 63(4): 482-93.</ref> <ref> I. Arnulf, J. M. Zeitzer, J. File, N. Farber, E. Mignot. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain, 2005 Dec; 128(Pt 12): 2763-76.</ref>  
Some studies suggest that KLS might be triggered by the infection or immune system. This is based on observation that many patients had such as fever, or cold before their KLS symptoms
started and Inflammation has also seen in certain area of the brain such as [[thalamus]], [[diencephalon]], and [[midbrain]]. Additionally a specific type of HLA antigen called DQB1*02 might
be related to KLS.<ref name="pmidPMID: 17761456">{{cite journal| author=BaHammam AS, GadElRab MO, Owais SM, Alswat K, Hamam KD| title=Clinical characteristics and HLA typing of a family with Kleine-Levin syndrome. | journal=Sleep Med | year= 2008 | volume= 9 | issue= 5 | pages= 575-8 | pmid=PMID: 17761456 | doi=10.1016/j.sleep.2007.06.015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17761456  }} </ref>


== Symptoms ==
=== Neuropathological Causes: ===
[[Hypersomnia]] is a primary symptom of KLS, and is present in all subjects.  Subjects are often treated initially for a sleeping disorder.  During a KLS episode, subjects often spend 18 hours a day asleep.  Another defining symptom of KLS is an altered mental state during the episode.  Subjects are hard to arouse from this sleep, and are irritable or aggressive when prevented from sleeping.  Subjects also frequently show [[cognitive impairment]]<ref> A. M. Landtblom, N. Dige, K. Schwerdt, P. Säfström, G. Granérus. Short-term memory dysfunction in Kleine-Levin syndrome. Acta Neurol Scand, 2003, Nov, 108(5): 363-7.</ref>, and can show confusion, [[amnesia]] for the event, [[hallucinations]], [[delusions]], or experience a dream-like state.  About 75% of KLS patients experience changes in eating behavior during episodes, with the majority of these exhibiting megaphagia.  Reports describe patients who will eat anything placed in front of them with very little discrimination.  Reports also describe consumption of excessive amounts of food, but KLS is distinct from [[bulimia]] since no purging occurs after binging. Almost half of KLS patients also experience some sort of hypersexual behavior during the event, including promiscuity, excessive masturbation, inappropriate sexual advances, and other risqué, atypical behavior.  Hypersexual behavior is more common in males than females, and is associated with a much longer disease course.<ref> C. H. Schenck, I. Arnulf, M. W. Mahowald. Sleep and sex: what can go wrong? A review of the literature on sleep related disorders and abnormal sexual behaviors and experiences. Sleep, 2007, Jun 1, 30(6): 683-702.</ref>  Other unusual compulsions reported during the event are also not uncommon.<ref> L. P. Justo, H. M. Calil, S. A. Prado-Bolognani, M. Muszkat. Kleine-Levin syndrome: interface between neurology and psychiatry. Arq Neuropsiquiatr, 2007, Mar, 65(1): 150-2.</ref>
Few researches suggest that this problem affect multiple parts of the brain for example a study
found that the diencephalic-hypothalamic malfunction which is caused by the tumor has the similar symptoms as KLS. This suggests that the problem of the hypothalamus and as well as other area of the brain such as temporal and frontal lobe might be involved.<ref name="pmidPMID: 28778233">{{cite journal| author=Al Suwayri SM, BaHammam AS| title=The "Known Unknowns" of Kleine-Levin Syndrome: A Review and Future Prospects. | journal=Sleep Med Clin | year= 2017 | volume= 12 | issue= 3 | pages= 345-358 | pmid=PMID: 28778233 | doi=10.1016/j.jsmc.2017.03.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28778233  }} </ref>


== Genetics ==
=== Other Factors: ===
There are no known genetic markers for KLS.  There is no protein or antibody markers available for a positive diagnosis of KLS.  Some researchers have explored hereditable immunity traits that may predispose individuals for KLS.  One such trial focused on a family of twelve in which the father and five children were all affected by KLS.  [[Human leukocyte antigen]] (HLA) typing revealed the father was identical to two of his children that were both affected by KLS.  Furthermore, all of his affected children shared one-half of his HLA antigens.<ref> A. S. BaHammam, M. O. GadElRab, S.M. Owais, K. Alswat, K. D. Hamam. Clinical characteristics and HLA typing of a family with Kleine-Levin syndrome. Sleep Med, 2008 Jul; 9(5): 575-8.</ref>
Seasonal change, mild infection, Alcohol use, head injury, physical strain, stress and lack of
sleep, vaccination, and SARS-CoV2 Vaccine are also considered as risk factors.<ref name="pmidPMID: 34094848">{{cite journal| author=Nasrullah A, Javed A, Ashraf O, Malik K| title=Possible role of COVID-19 in the relapse of Klein-Levin Syndrome. | journal=Respir Med Case Rep | year= 2021 | volume= 33 | issue=  | pages= 101445 | pmid=PMID: 34094848 | doi=10.1016/j.rmcr.2021.101445 | pmc=8164508 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34094848  }} </ref>


== Diagnosis ==
== Epidemiology and Demographics: ==
Diagnosis of KLS is very difficult since there are no symptoms that allow for a positive diagnosis.  KLS is instead a diagnosis of exclusion, where a doctor must first eliminate a long list of other conditions that could mimic the symptoms.  Because hypersomnia is the primary symptom, many patients are initially treated for a sleeping disorder.  Potential KLS patients are often referred to an endocrinologist early on to check for metabolic problems including [[diabetes]] and [[hypothyroidism]].  Several neurological disorders can also mimic KLS symptoms, but those can be positively diagnosed by [[MRI]]—including ones caused by a lesion, tumor, or inflammation.  [[Multiple sclerosis]] also has neurological components that can mimic the symptom profile for KLS, but this can also be detected by an MRI.
It is the rare problem and the prevalence of the diseases is 1-5 people per million people.


Once the origin of the problem is confirmed to be psychiatric, several more common conditions must first be considered.  The depressive periods of bipolar disorder are easily mistaken for KLS episodes, but [[bipolar disorder]] is characterized by the manifestation of a manic episode.  Successful diagnosis often relies on interviews with not only the patient, but their friends and family—since many bipolar patients would not characterize their own behavior as mania.  Hypersexual behavior is also a difficult symptom to diagnose accurately, since this is a taboo subject to approach during an interview.  Because of cultural attitudes, this information is often not communicated to the physician—and ends up being left out of the diagnosis.  [[Narcolepsy]] and [[Klüver-Bucy syndrome]] also produce very similar symptom profiles, but typically have different [[EEG]] readings from a KLS patient.  Before a final diagnosis can be made, all other possibilities must be carefully excluded, and the cluster of symptoms must fit with those commonly observed in KLS patients.<ref> W.M. Fisher MD. Telephone INTERVIEW. 6 Nov, 2008</ref>
=== Age: ===
These diseases affect teenagers mostly and adults are also affected.


== Treatment ==
=== Gender: ===
There is no definitive treatment for Kleine-Levin syndrome. [[Stimulants]], including [[amphetamines]], [[methylphenidate]], [[imipramine]] and [[modafinil]], administered orally, are used to treat sleepiness. Because of similarities between Kleine-Levin syndrome and certain mood disorders, [[lithium]]<ref> F. Muratori, N. Bertini, G. Masi. Efficacy of lithium treatment in Kleine-Levin syndrome. Eur Psychiatry, 2002, Jul, 17(4): 232-3.</ref> and [[carbamazepine]] may be prescribed. Responses to treatment have often been limited. This disorder needs to be differentiated from cyclic re-occurrence of sleepiness during the premenstrual period in teenage girls that may be controlled with [[hormonal contraception]]. There is no treatment for Kleine-Levin syndrome as of yet however, stimulants are often used to keep the patient awake. This does not alter their mental state. <ref>[http://www.ninds.nih.gov/disorders/kleine_levin/kleine_levin.htm Kleine-Levin Syndrome Information Page: National Institute of Neurological Disorders and Stroke (NINDS)<!-- Bot generated title -->]</ref>
This disease is observed in male more than females approximately 70-90% patients are male.


== Frequency and Duration of Episodes ==
=== Race: ===
A 2005 study of 168 KLS patients reported that in subjects where the disease terminates, the average age is 23 and the median duration is 4 years.  They reported no correlation between age at onset and disease duration.  Patients experienced an average of 12 episodes lasting an average of 12 days, although the range of symptoms reported varied from 2-130 episodes and lasted between 2.5 and 80 days.  Subjects experienced an average duration of 6 months between episodes, but this ranged from .5 to 72 months.  Subjects typically experienced less frequent and less intense attacks towards the end of the disease course, and the subject is considered cured if they do not experience an episode for 6 or more years.<ref> I. Arnulf, J. M. Zeitzer, J. File, N. Farber, E. Mignot. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain, 2005 Dec; 128(Pt 12): 2763-76.</ref>  
KLS found in various races and location around the world and it is most of the cases are reported in Ashkenazi Jews then other groups.<ref name="pmidPMID: 29397778">{{cite journal| author=Al Shareef SM, Almeneessier AS, Smith RM, BaHammam AS| title=The clinical characteristics of Kleine-Levin syndrome according to ethnicity and geographic location. | journal=Int J Neurosci | year= 2018 | volume= 128 | issue= 9 | pages= 842-848 | pmid=PMID: 29397778 | doi=10.1080/00207454.2018.1437037 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29397778  }} </ref>


== Prognosis ==
== Diagnosis: ==
Living with KLS can be a very serious affair.  Many patients report depression during one or more episodes.  While the major symptoms may seem innocent enough to some (copious amounts of sleeping, eating, and sexual behavior) the effects can be very debilitating.  At very least, KLS makes it difficult to maintain a normal job—and in some cases criminal charges have resulted from unrestrained sexual behavior.  Periodic binges associated with the episode can lead to weight gain, and KLS patients often exhibit an above-average BMI, but no mention of obesity is made in the literature. KLS patients also end up suffering from other’s psychosocial stigmas because they don’t understand some of the unusual activities resulting during an episode.  Many patients report embarrassing episodes from early in their adolescence before KLS was considered a viable diagnosis.<ref> C. H. Schenck, I. Arnulf, M. W. Mahowald. Sleep and sex: what can go wrong? A review of the literature on sleep related disorders and abnormal sexual behaviors and experiences. Although, the disorder is not fatal so people can live with it. It can mess up their lives sometimes if the excessive sleepiness interferes with (school, jobs etc) Sleep, 2007, Jun 1, 30(6): 683-702.</ref>
Kleine–Levin Syndrome (KLS) is uncommon and its symptoms can overlap with other problems, patients being evaluated for KLS should also be investigated for other possible causes. Evaluation should include a detailed medical history of the patient and their family, physical examination, and close observation of any fluctuations in [[cognitive]] and behavioral patterns. If any unusual findings are present, they may indicate a different diagnosis.<ref name="pmidPMID: 16230322">{{cite journal| author=Arnulf I, Zeitzer JM, File J, Farber N, Mignot E| title=Kleine-Levin syndrome: a systematic review of 186 cases in the literature. | journal=Brain | year= 2005 | volume= 128 | issue= Pt 12 | pages= 2763-76 | pmid=PMID: 16230322 | doi=10.1093/brain/awh620 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16230322  }} </ref>


==Eponym==
=== Diagnostic Criteria: ===
It is named for Willi Kleine and Max Levin. <ref> W. Kleine. Periodische Schlafsucht. Monatsschrift für Psychiatrie und Neurologie, 1925, 57: 285-320.</ref><ref>M. Levin. Periodic somnolence and morbid hunger: A new syndrome. Brain, Oxford, 1936, 59: 494-504.</ref>
It is diagnosed on the basis of pattern of excessive sleep, behavior and thinking International
Classification of Sleep Disorders (Third Edition; ICSD-3) present the diagnostic criteria for KLS that includes.<ref name="pmidPMID: 25367475">{{cite journal| author=Sateia MJ| title=International classification of sleep disorders-third edition: highlights and modifications. | journal=Chest | year= 2014 | volume= 146 | issue= 5 | pages= 1387-1394 | pmid=PMID: 25367475 | doi=10.1378/chest.14-0970 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25367475  }} </ref>


==References==
=== Episode of Excessive Sleep: ===
<references/>
Individual with disorder has at least two episodes of sleep and the duration of the sleep is more than the normal days, the duration for each episode fall from two days to five weeks.


== External links ==
=== Frequent episodes: ===
*[http://www.klsfoundation.org The KLS Foundation]
Episodes usually happen more than once a year and at least once every 18 months.
*{{NINDS|kleine_levin}}


{{CNS diseases of the nervous system}}
=== Normal between Episodes: ===
{{SIB}}
After each episodes patient have a normal mood behavior and thinking.


[[Category:Low priority]]
=== Symptoms between Episodes: ===
during the episodes patients must show at least one of following symptoms such as


* Thinking or memory problem
* Change in perspective
* Change in diet pattern (East a lot or not enough)
* Unusual behavior (such as hypersexuality)


=== Exclusion Of other causes: ===
Doctor have to make sure that the excessive sleepiness is not
caused by the other sleep problems, medical conditions, brain issue, mental health problem or due to medication or drug.


[[de:Kleine-Levin-Syndrom]]
=== Laboratory Findings: ===
[[fa:سندرم کلاین - لوین]]
Test should be done on the basis of symptoms and other possible diagnosis. There are no specific finding in urine sample while autoimmune cause are considered, CSF and blood test does not show sign of inflammation however a recent study identified some biomarkers that are helpful for the diagnosis of KLS. In CSF 28 protein was found to be different from healthy individual some proteins were higher (such as IL-34 and IGF-1), and others were lower (such as DKK4). In blood sample protein 141 was different changes in brain protein, especially in areas like pons and
[[gl:Síndrome Kleine-Levin]]
mid brain were observed and protein levels varied during and between the episodes.<ref name="pmidPMID: 35859339">{{cite journal| author=Hédou J, Cederberg KL, Ambati A, Lin L, Farber N, Dauvilliers Y | display-authors=etal| title=Proteomic biomarkers of Kleine-Levin syndrome. | journal=Sleep | year= 2022 | volume= 45 | issue= 9 | pages=  | pmid=PMID: 35859339 | doi=10.1093/sleep/zsac097 | pmc=9453623 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35859339  }} </ref>
[[id:Sindrom Kleine-Levin]]
[[no:Kleine-Levins syndrom]]
[[pl:Zespół Kleinego-Levina]]
[[fi:Kleine-Levinin oireyhtymä]]
[[sv:Kleine-Levins syndrom]]


{{WikiDoc Help Menu}}
=== Neuroimaging: ===
{{WikiDoc Sources}}
Ususlly MRI and CT do not show KLS related findings and functional imaging techniques (like fMRI) is considered useful for the evaluation process it shows abnormal results in KLS patient during and between the episodes the findings include abnormal blood flow at the thalamus and
hypothalamus and freontal region of the brain PET /CT is also used to find out the metabolic
activity which is usually lower in patients with KLS.<ref name="pmidPMID: 35735605">{{cite journal| author=Ortiz JF, Argudo JM, Yépez M, Moncayo JA, Tamton H, Aguirre AS | display-authors=etal| title=Neuroimaging in the Rare Sleep Disorder of Kleine-Levin Syndrome: A Systematic Review. | journal=Clocks Sleep | year= 2022 | volume= 4 | issue= 2 | pages= 287-299 | pmid=PMID: 35735605 | doi=10.3390/clockssleep4020025 | pmc=9221874 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35735605  }} </ref>
 
== Treatment: ==
As the etiology of the diseases is still unknown therefore the definitive treatment is not available
however supportive treatment is given to delay the duration of episodes and relieve the symptoms.
 
=== Pharmacotherapy: ===
Numerous medications are used for symptomatic treatment including stimulants, amantadine,[[antiepileptics]], [[antidepressants]], [[antipsychotics]], steroids, and [[clarithromycin]] some of these sows benefit but their long-term effectiveness is known due to their rarity according to the [[American Academy of Sleep Medicine|American Academy of Sleep]] (AASM) lithium is the conditional recombination because it can reduce the symptoms.<ref name="pmidPMID: 34743789">{{cite journal| author=Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD | display-authors=etal| title=Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. | journal=J Clin Sleep Med | year= 2021 | volume= 17 | issue= 9 | pages= 1881-1893 | pmid=PMID: 34743789 | doi=10.5664/jcsm.9328 | pmc=8636351 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34743789  }} </ref>
 
== Reference: ==

Latest revision as of 10:08, 7 September 2024

Historical Perspective:

KLS was first introduced by Willi Kleine in 1925 as a " periodic sleep disorder," focusing on the recurrent hypersomnia and hyperphagia. In 1936, Max Levin expanded the description by including the excessive hunger characteristic of the syndrome. The name "Kleine-Levin Syndrome" was proposed by Critchley and Hoffman in 1942, based on their observations, which included cases among naval personnel serving during World War II. Critchley provided a more precise definition of the syndrome, refining the diagnosis with his observations and contributing to a clearer understanding of the condition and proposed Kleine-Levin Syndrome as an official name of the disease.[1]

Pathophysiology:

In KLS, active symptoms are linked to decreased activity in the thalamus of the brain, which contributes to excessive sleep. This decrease in thalamic activity is also linked to other symptoms such as emotional blunting, increased sexual behavior, and a sense of detachment from reality. Patients who experience the disease onset more recently or have had more episodes in the past year often show reduced brain metabolism in the hippocampus and posterior brain regions.However, about half of the patients exhibit increased metabolic activity in the frontal areas of the brain. These changes in brain function not only explain the hypersomnia but also account for the behavioral and cognitive symptoms associated with the condition.

Symptoms:

The main feature of the disease is recurrent extreme sleepiness and during the episodes, they also experience, confusion, change in mood, behavior alteration, and feeling like things aren't real overeating symptoms vary from person to person.[2]

Causes:

The cause of the diseases is still unknown but some factors are still considered as the potential causes of the diseases such as genetic factors, infectious or immune-mediated causes,neuropathological Causes and other factors.[3]

Genetic factor:

The specific gene causing the KLS has not been identified yet but some literature suggests that genetics might be involved in the development of the diseases. There are many cases of KLS among Ashkenazi Jews and it often runs in families including (identical twins), the family members of Patients with KLS have a higher chance of developing conditions themselves. Indicating a possible genetic link. Reported literature suggested the TRANK1 gene which controls the body's internal clock and is also associated with bipolar and schizophrenia[4]

Infectious or immune-mediated cause:

Some studies suggest that KLS might be triggered by the infection or immune system. This is based on observation that many patients had such as fever, or cold before their KLS symptoms started and Inflammation has also seen in certain area of the brain such as thalamus, diencephalon, and midbrain. Additionally a specific type of HLA antigen called DQB1*02 might be related to KLS.[5]

Neuropathological Causes:

Few researches suggest that this problem affect multiple parts of the brain for example a study found that the diencephalic-hypothalamic malfunction which is caused by the tumor has the similar symptoms as KLS. This suggests that the problem of the hypothalamus and as well as other area of the brain such as temporal and frontal lobe might be involved.[2]

Other Factors:

Seasonal change, mild infection, Alcohol use, head injury, physical strain, stress and lack of sleep, vaccination, and SARS-CoV2 Vaccine are also considered as risk factors.[6]

Epidemiology and Demographics:

It is the rare problem and the prevalence of the diseases is 1-5 people per million people.

Age:

These diseases affect teenagers mostly and adults are also affected.

Gender:

This disease is observed in male more than females approximately 70-90% patients are male.

Race:

KLS found in various races and location around the world and it is most of the cases are reported in Ashkenazi Jews then other groups.[7]

Diagnosis:

Kleine–Levin Syndrome (KLS) is uncommon and its symptoms can overlap with other problems, patients being evaluated for KLS should also be investigated for other possible causes. Evaluation should include a detailed medical history of the patient and their family, physical examination, and close observation of any fluctuations in cognitive and behavioral patterns. If any unusual findings are present, they may indicate a different diagnosis.[8]

Diagnostic Criteria:

It is diagnosed on the basis of pattern of excessive sleep, behavior and thinking International Classification of Sleep Disorders (Third Edition; ICSD-3) present the diagnostic criteria for KLS that includes.[9]

Episode of Excessive Sleep:

Individual with disorder has at least two episodes of sleep and the duration of the sleep is more than the normal days, the duration for each episode fall from two days to five weeks.

Frequent episodes:

Episodes usually happen more than once a year and at least once every 18 months.

Normal between Episodes:

After each episodes patient have a normal mood behavior and thinking.

Symptoms between Episodes:

during the episodes patients must show at least one of following symptoms such as

  • Thinking or memory problem
  • Change in perspective
  • Change in diet pattern (East a lot or not enough)
  • Unusual behavior (such as hypersexuality)

Exclusion Of other causes:

Doctor have to make sure that the excessive sleepiness is not caused by the other sleep problems, medical conditions, brain issue, mental health problem or due to medication or drug.

Laboratory Findings:

Test should be done on the basis of symptoms and other possible diagnosis. There are no specific finding in urine sample while autoimmune cause are considered, CSF and blood test does not show sign of inflammation however a recent study identified some biomarkers that are helpful for the diagnosis of KLS. In CSF 28 protein was found to be different from healthy individual some proteins were higher (such as IL-34 and IGF-1), and others were lower (such as DKK4). In blood sample protein 141 was different changes in brain protein, especially in areas like pons and mid brain were observed and protein levels varied during and between the episodes.[10]

Neuroimaging:

Ususlly MRI and CT do not show KLS related findings and functional imaging techniques (like fMRI) is considered useful for the evaluation process it shows abnormal results in KLS patient during and between the episodes the findings include abnormal blood flow at the thalamus and hypothalamus and freontal region of the brain PET /CT is also used to find out the metabolic activity which is usually lower in patients with KLS.[11]

Treatment:

As the etiology of the diseases is still unknown therefore the definitive treatment is not available however supportive treatment is given to delay the duration of episodes and relieve the symptoms.

Pharmacotherapy:

Numerous medications are used for symptomatic treatment including stimulants, amantadine,antiepileptics, antidepressants, antipsychotics, steroids, and clarithromycin some of these sows benefit but their long-term effectiveness is known due to their rarity according to the American Academy of Sleep (AASM) lithium is the conditional recombination because it can reduce the symptoms.[12]

Reference:

  1. ↑ Al Suwayri SM (2016). "Kleine-Levin syndrome. Familial cases and comparison with sporadic cases". Saudi Med J. 37 (1): 21–8. doi:10.15537/smj.2016.1.12992. PMC 4724674. PMID 26739970 PMID: 26739970 Check |pmid= value (help).
  2. ↑ 2.0 2.1 Al Suwayri SM, BaHammam AS (2017). "The "Known Unknowns" of Kleine-Levin Syndrome: A Review and Future Prospects". Sleep Med Clin. 12 (3): 345–358. doi:10.1016/j.jsmc.2017.03.012. PMID 28778233 PMID: 28778233 Check |pmid= value (help).
  3. ↑ AlShareef SM, Smith RM, BaHammam AS (2018). "Kleine-Levin syndrome: clues to aetiology". Sleep Breath. 22 (3): 613–623. doi:10.1007/s11325-017-1617-z. PMC 6133116. PMID 29532411 PMID: 29532411 Check |pmid= value (help).
  4. ↑ Ambati A, Hillary R, Leu-Semenescu S, Ollila HM, Lin L, During EH; et al. (2021). "Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci". Proc Natl Acad Sci U S A. 118 (12). doi:10.1073/pnas.2005753118. PMC 7999876 Check |pmc= value (help). PMID 33737391 PMID: 33737391 Check |pmid= value (help).
  5. ↑ BaHammam AS, GadElRab MO, Owais SM, Alswat K, Hamam KD (2008). "Clinical characteristics and HLA typing of a family with Kleine-Levin syndrome". Sleep Med. 9 (5): 575–8. doi:10.1016/j.sleep.2007.06.015. PMID 17761456 PMID: 17761456 Check |pmid= value (help).
  6. ↑ Nasrullah A, Javed A, Ashraf O, Malik K (2021). "Possible role of COVID-19 in the relapse of Klein-Levin Syndrome". Respir Med Case Rep. 33: 101445. doi:10.1016/j.rmcr.2021.101445. PMC 8164508 Check |pmc= value (help). PMID 34094848 PMID: 34094848 Check |pmid= value (help).
  7. ↑ Al Shareef SM, Almeneessier AS, Smith RM, BaHammam AS (2018). "The clinical characteristics of Kleine-Levin syndrome according to ethnicity and geographic location". Int J Neurosci. 128 (9): 842–848. doi:10.1080/00207454.2018.1437037. PMID 29397778 PMID: 29397778 Check |pmid= value (help).
  8. ↑ Arnulf I, Zeitzer JM, File J, Farber N, Mignot E (2005). "Kleine-Levin syndrome: a systematic review of 186 cases in the literature". Brain. 128 (Pt 12): 2763–76. doi:10.1093/brain/awh620. PMID 16230322 PMID: 16230322 Check |pmid= value (help).
  9. ↑ Sateia MJ (2014). "International classification of sleep disorders-third edition: highlights and modifications". Chest. 146 (5): 1387–1394. doi:10.1378/chest.14-0970. PMID 25367475 PMID: 25367475 Check |pmid= value (help).
  10. ↑ Hédou J, Cederberg KL, Ambati A, Lin L, Farber N, Dauvilliers Y; et al. (2022). "Proteomic biomarkers of Kleine-Levin syndrome". Sleep. 45 (9). doi:10.1093/sleep/zsac097. PMC 9453623 Check |pmc= value (help). PMID 35859339 PMID: 35859339 Check |pmid= value (help).
  11. ↑ Ortiz JF, Argudo JM, Yépez M, Moncayo JA, Tamton H, Aguirre AS; et al. (2022). "Neuroimaging in the Rare Sleep Disorder of Kleine-Levin Syndrome: A Systematic Review". Clocks Sleep. 4 (2): 287–299. doi:10.3390/clockssleep4020025. PMC 9221874 Check |pmc= value (help). PMID 35735605 PMID: 35735605 Check |pmid= value (help).
  12. ↑ Maski K, Trotti LM, Kotagal S, Robert Auger R, Rowley JA, Hashmi SD; et al. (2021). "Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline". J Clin Sleep Med. 17 (9): 1881–1893. doi:10.5664/jcsm.9328. PMC 8636351 Check |pmc= value (help). PMID 34743789 PMID: 34743789 Check |pmid= value (help).
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