Kleine–Levin syndrome (KLS) is a rare sleep disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Many patients also experience hyperphagia, hypersexuality and other. Kleine–Levin syndrome (KLS) is a rare disorder with symptoms that include hypersexuality, hypersomnia, Kleine–Levin syndrome, megaphagia, periodic. Nearly half of the patients had symptoms consistent with hypersexuality during episodes, and it.
Kleine-Levin syndrome (KLS) is a rare neurological disorder of unknown origin patients experience hyperphagia (66% of patients), hypersexuality (53% of. Kleine–Levin syndrome (KLS) is a rare disorder with symptoms that include hypersexuality, hypersomnia, Kleine–Levin syndrome, megaphagia, periodic. Kleine-Levin Syndrome (KLS) is a rare and complex neurological disorder Instances of uninhibited hyper-sexuality during an episode have also been.
Nearly half of the patients had symptoms consistent with hypersexuality during episodes, and it. Kleine–Levin syndrome (KLS) is a rare sleep disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Many patients also experience hyperphagia, hypersexuality and other. Kleine-Levin syndrome (KLS), known also as recurrent hypersomnia or periodic and cognitive disturbances, hyperphagia and in some cases hypersexuality.
Kleine-Levin syndrome KLSknown also as kleine hypersomnia or periodic hypersomnolence, kleine a rare sleep disorder with the prevalence 1—2 cases per million, more frequently found in hypersexuality Jewish population.
The main features are intermittent periods of hypersomnolence accompanied by behavioral and cognitive disturbances, hyperphagia kleine in hypersexuality cases hypersexuality. According to ICSD-3, four diagnostic criteria must be met:. Kleine-Levin Syndrome. You are here: Home Kleine-Levin Syndrome. Kleine-Levin Syndrome Kleine-Levin syndrome KLSknown also as recurrent hypersomnia or periodic hypersomnolence, is a rare sleep disorder with the prevalence 1—2 cases syndrime million, more frequently found levin the Jewish population.
According to Syndrome, four diagnostic criteria must be met: The patient experiences at least two recurrent episodes of excessive sleepiness and sleep duration, each persisting levin 2 days to 5 weeks. Episodes recur usually more than once a year and at least once every 18 months. The patient must demonstrate syndrome least one of the following during episodes: Cognitive levin Altered perception Eating disorder hyperphagia or anorexia Disinhibited behavior such as hypersexuality The hypersomnolence and related symptoms are not better explained by levvin sleep disorder; other medical, neurologic, or psychiatric disorders syndrome bipolar disorder ; or the use of drugs or medications.
The patient must demonstrate at least one of the following during episodes: Cognitive dysfunction Altered perception Eating disorder hyperphagia or anorexia Disinhibited behavior such as hypersexuality The hypersomnolence and related symptoms are not better explained by another sleep disorder; other medical, neurologic, or psychiatric disorders especially bipolar disorder ; or the use of drugs or medications.
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 to episodes and lasted between 2.
Subjects experienced an average duration of 6 months between episodes, but this ranged from 0. Subjects typically experienced less frequent and less intense attacks toward the end of the disease course, and the subject is considered cured if they do not experience an episode for 6 or more years. The median disease duration is 10 years in patients without hypersexuality, but 21 years in patients with hypersexuality. The duration also appears to be more years for patients initially struck as adults.
Women had a longer disease course than men, despite a comparable age at KLS onset and an absence of differences in the duration of episodes and symptoms-free intervals. Women had the same frequency of megaphagia and psychotic symptoms, but a lower frequency of hypersexuality and cognitive impairment. In contrast, the age at KLS onset, the presence of megaphagia, cognitive disturbances, psychotic signs, and hypersexuality did not influence the course of the disease.
KLS is an intriguing, severe, homogenous disease, known for more than a century, with defined clinical features, but no clear cause or treatment. Therefore, for studies on KLS was done exclusively with case reports or case series.
There are limited systemic study on comparing well-defined KLS with control group in terms of phenomenology, biological cause, and lists of investigations to identify disease and its management. However, few study findings suggest the possible Jewish predisposition, occasional familial clustering, and the association with infectious triggering factors suggesting that KLS is caused by environmental factors acting on a vulnerable genetic background.
Recent methods of radiological investigation, such as SPECT, indicate that the brain dysfunction could be larger than expected, and encompass both cortical and subcortical and especially thalamus and hypothalamus areas. This general picture and the fluctuating symptomatology in KLS are consistent with the recent report of an HLA association in KLS and the possibility of an autoimmune mediation of the disorder.
Due to rarity of disorder, it is difficult to identify underlying biological cause. In future, we need further research on genetic etiology and management of this disorder. Source of Support: Nil. Conflict of Interest: Nil. National Center for Biotechnology Information , U. Ann Indian Acad Neurol. Santosh Ramdurg.
Author information Article notes Copyright and License information Disclaimer. For correspondence: Dr. E-mail: moc. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract Kleine—Levin syndrome KLS is a rare sleep disorder mainly affecting teenage boys in which the main features are intermittent hypersomnolence, behavioral and cognitive disturbances, hyperphagia, and in some cases hypersexuality.
Keywords: Hypersomnia, hypersexuality, Kleine—Levin syndrome, megaphagia, periodic. Introduction Kleine—Levin syndrome KLS is a rare disease characterized by recurrent episodes of hypersomnia and to various degrees, behavioral or cognitive disturbances, compulsive eating behavior, and hypersexuality. Epidemiology The exact prevalence of KLS is unknown, but it is considered a very rare disease, possibly affecting one in a million.
Etiology An underlying hypothalamic pathology is suggested by the critical role of this structure in regulating sleep, appetite, and sexual behaviors; however, no consistent hypothalamic abnormalities have been identified.
Clinical Presentation Hypersomnia Hypersomnia, a major clinical symptom of KLS, is mandatory for diagnosis and was present in all cases. Cognitive Disturbances Majority of patients had cognitive disturbances such as confusion, concentration, attention, and memory defects. Eating Behavior Disorders Three quarters of the patients had changes in eating behaviors during episodes. Mood Disorders and Irritability Half of the patients had a depressive mood during episodes particularly in women.
Hypersexuality and Other Compulsive Behaviors Nearly half of the patients had symptoms consistent with hypersexuality during episodes, and it was significantly more frequent in men than in women.
Derealization, Hallucination, and Delusion A feeling of unreality surroundings seemed wrong, distorted or unreal, as in a dream or of disconnected thinking during episodes was reported by most patients and felt to be the most specific symptom of the syndrome. Personal and Family Medical History Birth history in few individuals revealed long labor, hypoxia, premature, or postmature birth. Open in a separate window. Diagnosis Diagnosis of KLS is very difficult since there are no symptoms that allow for a positive diagnosis.
Investigation Clinical examination was unremarkable in all cases with primary KLS. Cerebrospinal Fluid Analysis CSF analysis is done when infectious etiology was the possible cause for recurrent hypersomnia.
Electroencephalograms and Brain Imaging Three-fourth of the patients had a abnormal EEG during episodes, but this is not conclusive, nonspecific and by this we can barely rule-out possibility of epilepsy. Treatment There is no definitive treatment for Kleine—Levin syndrome during episode as well as interepisodic period. Table 2 Treatments used in patients with Kleine—Levin syndrome and reported effects[ 7 , 36 ].
Course and Prognosis Kleine—Levin syndrome has a benign clinical course, with spontaneous disappearance of symptoms. Conclusion KLS is an intriguing, severe, homogenous disease, known for more than a century, with defined clinical features, but no clear cause or treatment. References 1. Hauri P, editor. American Academy of Sleep Medicine. Kleine W. Periodische schlafsucht. Monats Psychiatr Neurol. Levin M. Arch Neurol Psychiat. Periodic somnolence and morbid hunger: A new syndrome.
Critchley M. Periodic hypersomnia and megaphagia in adolescent males. Thorpy MJ. Diagnostic Classification Steering Committee. American Sleep Disorders Association. Kleine-Levin syndrome: A systematic review of cases in the literature. Clinical and polysomnographic characteristics of 34 patients with Kleine-Levin syndrome. J Sleep Res.
Huang YS, Arnulf I. The Kleine-Levin Syndrome. Sleep Med Clin. A case report of Kleine-Levin syndrome in an adolescent girl. Familial Kleine-Levin syndrome: Two siblings with unusually long hypersomnic spells. The neurological signs that were observed between the episodes were various, with very few commonalities between patients. They included objective sensory disturbances of the extremities Wilder, ; impaired verbal abilities Takrani and Cronin, ; bilateral pyramidal signs and mental retardation Livrea et al.
Sleep recordings were performed in half of these patients and yielded the same abnormalities as in primary cases, including short REM sleep latency in two cases Drake, ; Berthier et al. Pharmacological therapy 18 trials was initiated in 8 of 18 patients.
As in primary cases, antidepressants 3 trials , neuroleptics 2 trials and a sedative 1 trial had no effect, while carbamazepine and lithium were associated with a reduction but not an ending in the number of attacks in 1 of 3 patients and 3 of 4 patients, respectively.
This systematic review reports on the largest number of KLS patients ever presented, with inclusion of all non-English language articles. The striking commonality of symptoms across patients is again demonstrated, suggesting a unique disease entity. Episodic hypersomnia and cognitive disturbances may constitute the core abnormality, while behavioural, eating and sexual disturbances are more variable and may occur only in a subset of episodes even within single patients.
Age of onset, sex-ratio, triggering factors and frequency of symptoms are similar to two recent small case series reported in Europe by Dauvilliers et al. The analysis shows, for the first time, a worldwide distribution for KLS. Of note, one-sixth of the patients reported were Israeli, suggesting either a publication bias or a higher vulnerability in subjects with Jewish heritage. Follow-up prospective studies will be needed to shed light on potential ethnic differences.
The occurrence of an infection at the disease onset in more than two-thirds of the patients, already stressed by some authors, seems too frequent and too closely associated for KLS to be due to chance. Unfortunately, however, in rare cases where an infectious agent was identified, it differed from one patient to another. These agents may thus decompensate a previously existing disease, or a coexisting infection with another yet undetected infectious agent may be responsible.
Additional work in this area is needed as the studies of some notable infectious agents known to cause confusion, hypersomnia and various neuro-psychiatric symptoms such as Whipple's disease, malaria, California encephalitis or encephalitis lethargica-like agents Dale et al.
Infection, head trauma and alcohol are all known to increase the blood—brain barrier permeability Rapoport et al. This study is also the first to report on the median duration of the disease, a relatively longer than expected 4—8 years, which is an important variable to report to patients first presenting with the disease. Four years was a lower estimate based on patients with disease terminated at time of publication other subjects with longer course duration are more likely not to be published , while 8 years may be slightly overestimated if patients lost in follow-up are generally cured.
One long-term follow-up study via phone or in-person interviews reported that 25 patients were in good health several years after the cessation of their KLS episodes, suggesting that complete recovery and a good prognosis is the rule for KLS Gadoth et al.
They did not, however, report on the final duration of the disease. If confirmed in a series with long-term follow-up, it would raise the idea that some rare patients may present permanent lesions, which would support early aggressive medical intervention Landtblom et al.
The older age in secondary KLS is probably due to the presence of stroke as a cause in five patients, a disease that affects preferentially older subjects. These lesions would only facilitate KLS, causing longer and more frequent episodes.
The evaluation of treatment, based on case-reports, was hard to assess because of the unpredictable spontaneous course of the disease and of the absence of placebo-controlled studies. It was evaluated in a large population of patients, and, as generally predicted, results were extremely disappointing. Amphetamine-stimulants significantly improved sleepiness Table 4 but not the other more serious symptoms, suggesting a very imperfect therapeutic relief. The potential benefit of lithium at preventing relapses Table 4 , only administered in 29 cases, if confirmed, should be balanced against its known difficulty of use and unfavourable side-effect profile.
We also noted that antiepileptic mood stabilizers especially carbamazepine were commonly prescribed, probably based on the possible efficacy of lithium, but results were similar to no drug treatment, strongly suggesting that this practice has no justification.
Antidepressant therapies were similarly ineffective. We believe that additional therapeutic trials using other medications, such as immunosuppressive or novel antiviral agents, with double-blind placebo-controlled multicentre design, are warranted.
There are several limitations to our study that are inherent to any systematic review. Only published case-reports are considered, and, even if KLS cases are more likely to be published when compared to other diseases because of the rarity of the syndrome and its striking symptoms, the published cases may not be representative of the general KLS population.
This could lead to a seemingly apparent homogeneity of the published disease. Importantly, however, it is an accepted fact that even recurrent hypersomnia without ancillary symptoms is a rare occurrence in clinical practice. The second limitation pertains to data available in published studies. For the same reason, it is possible that the apparent success of any treatment will be more often published than a failure to respond.
This study also highlights possible pathophysiological mechanisms for the disorder. Partial complex epilepsy, a condition that can produce episodes of recurrent abnormal behaviour, can be ruled out. The poor response of the condition to antiepileptic therapy also substantiates this hypothesis. A local brain lesion is also unlikely, considering the polymorphism of the symptomatology.
Finally, EEG, brain flow SPECT, or neuropathological data showed that frontal, temporal and sometimes occipital and parietal lobes can be involved, not to mention the thalamus Huang et al.
The finding of a possible Jewish predisposition, occasional familial clustering, and the association with infectious triggering factors suggest that KLS is due to environmental factors acting on a vulnerable genetic background. This general picture and the fluctuating symptomatology in KLS are consistent with the recent report of an HLA association in KLS and the possibility of an autoimmune mediation of the disorder.
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Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. Symptoms of KLS. Cases with secondary KLS. Kleine—Levin syndrome: a systematic review of cases in the literature I. Correspondence to: I. Oxford Academic. Google Scholar. Cite Citation.
Permissions Icon Permissions. Abstract Kleine—Levin syndrome KLS is a rare disorder with symptoms that include periodic hypersomnia, cognitive and behavioural disturbances. Open in new tab Download slide. Table 1. Open in new tab. Table 2. Table 3. Table 4. Treatments used in patients with Kleine—Levin syndrome and reported effects. Table 5. Differences between patients with primary and secondary Kleine—Levin syndrome. American Academy of Sleep Medicine.
Argentino C, Sideri G. Kleine—Levin syndrome. Riv Neurol. Rev Neurol. Kleine—Levin syndrome in an 82 year old man. Ital J Neurol Sci. Recurrent hypersomnia in two adolescent males with Asperger's syndrome.
Billiard M, Carlander B. Wake disorders. Primary wake disorders. Rev Neurol Paris. A menstruation-linked periodic hypersomnia. Kleine—Levin syndrome or new clinical entity? A propos of a case. Arch Fr Pediatr. Bouchard C, Levasseur M. Brierre de Boismont A. Des hallucinations. Third edition. Cante C, Marocchino R. Kleine—Levin syndrome: observations during a course of hypothymic episodes. Osp Psichiatr. A pathologic basis for Kleine—Levin syndrome. Arch Neurol. Chaudhry HR. Clinical use of moclobemide in Kleine—Levin syndrome.
Br J Psychiatry. Neuroendocrine evaluation in Kleine—Levin syndrome: evidence of reduced dopaminergic tone during periods of hypersomnolence. Dis Nerv Syst. Kleine—Levin syndrome 15 years later.
Aust N Z J Psychiatry. Critchley M, Hoffman H. The syndrome of periodic somnolence and morbic hunger Kleine—Levin syndrome. Critchley M. Periodic hypersomnia and megaphagia in adolescent males. Crumley FE. Valproic acid for Kleine—Levin syndrome. Cuetter AC.
Sleep apnea and the Kleine—Levin syndrome. Mil Med. Report of a case. Arq Neuropsiquiatr. Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Kleine—Levin syndrome: an autoimmune hypothesis based on clinical and genetic analyses. CSF hypocretin-1 levels in narcolepsy, Kleine—Levin syndrome, and other hypersomnias and neurological conditions.
J Neurol Neurosurg Psychiatry. A case of hypersomnia resembling Kleine—Levin syndrome. Neurol Neurochir Pol. Drake ME Jr. Kleine—Levin syndrome after multiple cerebral infarctions. Duffy JP, Davison K. A female case of the Kleine—Levin syndrome. Elian M. Periodic hypersomnia. Electroencephalogr Clin Neurophysiol. Clinical features of Kleine—Levin syndrome with localized encephalitis. Ferguson BG. Kleine—Levin syndrome: a case report.
J Child Psychol Psychiatry. Disturbed hypothalamic-pituitary axis in idiopathic recurring hypersomnia syndrome. Acta Neurol Scand. The Kleine—Levin syndrome. Case report and review of the literature. Am J Dis Child. Kleine—Levin syndrome—recurrent hypersomnia of male adolescents. Ann Med Psychol Paris. Periodic hypersomnia: case-report with biochemical and EEG findings. Fukunishi I, Hosokawa K. A female case with the Kleine—Levin syndrome and its physiopathologic aspects.
Jpn J Psychiatry Neurol. Episodic hormone secretion during sleep in Kleine—Levin syndrome: evidence for hypothalamic dysfunction. Brain Dev. Clinical and polysomnographic characteristics of 34 patients with Kleine—Levin syndrome.
J Sleep Res. Gallinek A. The Kleine—Levin syndrome: hypersomnia, bulimia, and abnormal mental states. World Neurol. Some further observations. Kleine—Levin syndrome in a boy with Prader-Willi syndrome. George HR. A case of the Kleine—Levin syndrome of long duration.
Gilbert GJ. Periodic hypersomnia and bulimia. Gillberg C. Kleine—Levin syndrome: unrecognized diagnosis in adolescent psychiatry. Goldberg MA. The treatment of Kleine—Levin syndrome with lithium. Can J Psychiatry. A case with EEG evidence of periodic brain dysfunction. Haberland C, Weissman S.