Recurrent Episodes Of Hypersomnia Research Articles

Sleep Disorder Kleine-Levin Syndrome (KLS) Joins the List of Polygenic Brain Disorders Associated with Obstetric Complications.

Kleine-Levin Syndrome is a rare neurological disorder with onset typically during adolescence that is characterized by recurrent episodes of hypersomnia, behavioral changes, and cognitive abnormalities, in the absence of structural changes in neuroimaging. As for many functional brain disorders, the exact disease mechanism in Kleine-Levin Syndrome is presently unknown, preventing the development of specific treatment approaches or protective measures. Here we review the pathophysiology and genetics of this functional brain disorder and then present a specific working hypothesis. A neurodevelopmental mechanism has been suspected based on associations with obstetric complications. Recent studies have focused on genetic factors whereby the first genome-wide association study (GWAS) in Kleine-Levin Syndrome has defined a linkage at the TRANK1 locus. A Gene x Environment interaction model involving obstetric complications was proposed based on concepts developed for other functional brain disorders. To stimulate future research, we here performed annotations of the genes under consideration for Kleine-Levin Syndrome in relation to factors expected to be associated with obstetric complications. Annotations used data-mining of gene/protein lists related to for hypoxia, ischemia, and vascular factors and targeted literature searches. Tentative links for TRANK1, four additional genes in the TRANK1 locus, and LMOD3-LMO2 are described. Protein interaction data for TRANK1 indicate links to CBX2, CBX4, and KDM3A, that in turn can be tied to hypoxia. Taken together, the neurological sleep disorder, Kleine-Levin Syndrome, shows genetic and mechanistic overlap with well analyzed brain disorders such as schizophrenia, autism spectrum disorder and ADHD in which polygenic predisposition interacts with external events during brain development, including obstetric complications.

Self-representation in Kleine-Levin syndrome: a single case fMRI study

ABSTRACT Kleine-Levin syndrome (KLS) is characterized by recurrent episodes of hypersomnia, compulsive hyperphagia, disinhibition, hypersexuality and self modifications. To investigate the Self, we used afunctional magnetic resonance imaging paradigm evaluating Self-reference processing (SRP) and Self-reference effect (SRE) in a17-year-old male adolescent at the end of an episode. We observed enhanced activations in right hemisphere and posterior areas– associated with physical Self representations– during the SRP condition, while during the SRE condition, enhanced activations in bilateral but prevailing left frontal areas– associated with the conceptual Self. These results suggest amodified Self during aKLS episode being more physically grounded.

Conversion Reaction after a Traumatic Brain Injury

KLS, also called recurrent hypersomnia, is a sleep disorder characterized by recurrent episodes of hypersomnia associated with cognitive and behavioral disturbances such as confusion, derealisation, apathy, compulsive eating, and hypersexuality. In this article, we aim to present a case with a history of traumatic brain injury who had been suffering from memory disturbance and came in an unresponsive state. He met several therapists and hospitalized several times. Through reviewing his history, we point out some diagnosis and discuss the probable effect of stressful life events on such patients with impaired memory system. The patient has received these medications during hospitalization in neurology ward pantoprazole 40mg po Qd, amantadine 100mg po BID, modafinil 100mg po TID in addition to diazepam and heparin in bedside. In this case, combination therapy and using hypnosis with family support and cooperation in several medical visits seems to be effective for early treatment.

Kleine–Levin syndrome – a diagnostic challenge? Case report

Kleine–Levin syndrome is a rare disease (1–2 cases per million inhabitants) characterised by recurrent episodes of hypersomnia with accompanying hyperphagia, hypersexuality and behavioural abnormalities such as aggression, irritability and disorientation. The diagnosis is based on clinical criteria, after ruling out other causes of hypersomnia. There are no lesions in brain imaging studies while EEG demonstrates slowing of bioelectrical activity in some cases. Kleine–Levin syndrome has a self-limiting course with symptoms becoming milder over time until they disappear completely. The pathogenesis includes hypothalamic pathology or autoimmune background (association with certain human leukocyte antigens). This article presents a young patient with a typical clinical picture of Kleine–Levin syndrome. Due to its rare occurrence, the knowledge about this disease entity is not common – the correct diagnosis was made a year after the onset of first symptoms.

A Polysomnography Study of Kleine-Levin Syndrome in a Single Center.

Background:Kleine–Levin syndrome (KLS) is a rare sleep disorder characterized by recurrent episodes of hypersomnia. Polysomnographic (PSG) researches of KLS have been reported only in few publications in the past decades. This study aimed to investigate the characteristics of PSG of KLS.Methods:This study, which was conducted from March 2010 to July 2014, included seven patients diagnosed with KLS in the Sleep and Wake Disorder Center of Huashan Hospital, Fudan University (Shanghai, China). PSG and multiple sleep latency tests (MSLT) were performed during their episodes and the results were evaluated.Results:Five of the seven patients were males. The mean age at KLS onset was 15.6 ± 3.6 years. The number of episodes ranged from 2 to 7. The duration of episodes lasted from 4 to 11 days. The sleep architecture and proportion were normal in most of the patients. The average value of mean sleep latency was 6.9 ± 4.1 min. No sleep-onset rapid eye movement (SOREM) was detected in three of the patients, whereas one patient experienced one period of SOREM, and such episodes occurred twice in other two patients.Conclusions:We found that sleep architecture and proportion were normal in most KLS patients. However, the results of PSG and MSLT had no specificity for KLS patients.

Missing the Diagnosis in a Young Woman with Repeated Hospital Admissions: A Case Report

Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by various symptoms, such as recurrent episodes of hypersomnia, cognitive abnormalities, psychiatric symptoms, hyperphagia, and be...

Pharmacological treatment for Kleine-Levin syndrome.

This is an updated version of the original Cochrane review, published in 2009, Issue 2.Kleine-Levin syndrome (KLS) is a rare disorder that mainly affects adolescent men. It is characterised by recurrent episodes of hypersomnia, usually accompanied by hyperphagia, cognitive and mood disturbances, abnormal behaviour, such as hypersexuality, and signs of dysautonomia.In 1990, the diagnostic criteria for Kleine-Levin syndrome were modified in the International Classification of Sleep Disorders, where KLS was defined as a syndrome comprised of recurring episodes of undue sleepiness lasting some days, which may or may not be associated with hyperphagia and abnormal behaviour. According to the International Classification of Sleepiness Disorders, 3rd version (ICSD-3), revised in 2014, the Kleine-Levin syndrome is a disorder characterized by recurrent episodes of hypersomnia that last from two days to four weeks, with at least annual recurrence, and hyperphagia (rapid consumption of a large amount of food), usually with onset in early adolescence in males but occasionally in later life and in women. A monosymptomatic form of the disorder with hypersomnia only can occur without binge eating or hypersexuality.The cause of Kleine-Levin syndrome remains unknown, and several treatment strategies have been used. Some medications have been reported to provide benefit in the treatment of patients with KLS, but because of the rarity of the condition, no long-term follow-up therapies have yet been described. This review aimed to evaluate:1. whether pharmacological treatment for Kleine Levin syndrome was effective and safe.2. which drug or category of drugs was effective and safe. For the latest update, we searched the following sources: the Cochrane Epilepsy Group Specialized Register (7 April 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online CRSO (7 April 2016); MEDLINE (1946 to April 2016); LILACS (7 April 2016); ClinicalTrials.gov (7 April 2016); WHO International Clinical Trials Registry Platform ICTRP (7 April 2016); reference lists of sleep medicine textbooks; review articles and reference lists of articles identified by the search strategies. All randomised controlled trials (RCTs) and quasi-randomised controlled trials looking at pharmacological interventions for Kleine-Levin syndrome were eligible. We had planned to include both parallel-group and cross-over studies. Two review authors (MMO and CC) had planned to extract the data reported in the original articles. No studies met the inclusion criteria for this systematic review. Therapeutic trials of pharmacological treatment for Kleine-Levin syndrome with a double-blind, placebo-controlled design are needed.

Recurrent hypersomnia: Kleine-Levin syndrome

IntroductionKleine-Levin syndrome was first described by Kleine in 1925 and elaborated on by Levi in 1936. It is an infrequent syndrome that predominantly affects to teenagers, and boys are four times more likely to be affected than girls. It is rare for patients over 30 years although some cases have been reported. Kleine-Levin syndrome is a recurrent hypersomnia characterized by episodes of hypersomnia lasting for 2 days to 4 weeks associated with symptoms of hyperphagia, hypersexuality and cognitive impairment. It can be accompanied by other abnormal behavior such as aggression, personality changes and irritability. Deficits are resolved between episodes.Case reportIt is presented the case report of a patient that suffers from recurrent episodes of hypersomnia associated with hyperphagia and abnormal behavior.ElectroencephalographyEEG demonstrates slowing of drowsiness and a decrease in REM sleep. The test of multiple sleep latency is abnormal and the rest of complementary test are normal.DiagnosisF51.1 Recurrent hypersomnia (Kleine-Levin syndrome) [307.44].DiscussionKleine-Levin syndrome is an intriguing, severe and homogenous disease with no obvious cause or treatment. Treatment is generally supportive. It should be considered in any teenager presenting with recurrent episodes of hypersomnia concurrent with cognitive changes or disinhibition.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Rare Case of Kleine-Levin Syndrome with Mega Cisterna Magna

Kleine-Levin syndrome (KLS) is an uncommon syndrome characterized by recurrent episodes of hypersomnia, behavioural and/or cognitive disturbances, abnormal eating and hypersexual behaviour. The diagnosis is clinical and requires a high index of suspicion and exclusion of other neurological conditions and sleep disorders. We report a case of 15-year-old male who had recurrent episodes of hypersomnia with hyperphagia, hypersexuality, disinhibition and cognitive dysfunction. His brain CT scan shows Mega cistern magna and EEG during the episode shows sharp and spike wave in both frontal and temporal lobes with secondary generalization. The patient became symptom-free after receiving Na Valporate.

The Kleine-Levin Syndrome: A Rare Disease with Often Delayed Diagnosis-A Report of Two Cases in the Department of Neurology of the University Hospital of Cocody (Côte d'Ivoire).

The Kleine-Levin syndrome is a rare pathology characterized by recurrent episodes of hypersomnia associated with behavioral and cognitive disorders with, among others, hyperphagia and hypersexuality. The disease mainly affects young males. A few studies mention cases that occurred in Africa, especially in Côte d'Ivoire. In this paper, we report the very first two cases observed in the Neurology Department of the University Hospital of Cocody. The diagnosis was clinical, based on the recurrence of hypersomnia, cognitive and behavioral disorders during the periods of hypersomnia, and the return of patients to normal state between episodes. This diagnosis was delayed due to failure to understand the pathology, thereby leading patients to wandering. In fact, the two patients were consulted, respectively, 3 years and 6 years after the hypersomnia began. The objective was to report the very first cases observed in the Neurology Department of the University Hospital of Cocody, Côte d'Ivoire.

Kleine-Levin syndrome in 120 patients: differential diagnosis and long episodes.

Kleine-Levin syndrome is a rare disease characterized by recurrent episodes of hypersomnia with behavioral and cognitive disturbances. We aimed at describing the diagnosis procedure, risk factors, and severe forms. In consecutive patients referred for suspected Kleine-Levin syndrome, we detailed differential diagnoses, and atypical and secondary cases, compared typical patients with healthy subjects, and examined the characteristics of patients with prolonged (>30 days) episodes. Among 166 referred patients, 120 had typical primary Kleine-Levin syndrome (syndrome secondary to brain diseases; n = 4, atypical syndrome, n = 7; differential diagnoses that were mostly psychiatric, n = 29; incomplete information, n = 6). The prevalence in France was 1.8 per million. The patients were often male (64%) and had more frequent birth and developmental abnormalities (45%) than controls (despite normal karyotypes), and most (80%) had teenage onset, with no difference between patients with prolonged (n = 34) and short (n = 85) episodes. In patients with prolonged episodes, the durations of the first episode (32 ± 33 vs 11 ± 6 days) and subsequent episodes were longer (mean episode duration = 23 ± 19 vs 10 ± 3 days) and the disease course tended to be longer (9 ± 6 vs 6 ± 4 years). During episodes, patients with prolonged episodes had shorter sleep time, higher levels of anxiety, increased agitation, and more feelings of disembodiment and amnesia. Between episodes, they were more tired, needed more naps, fell asleep more rapidly, and had higher anxiety/depression scores. Mental disorders are frequent differential diagnoses of Kleine-Levin syndrome. One-third of patients have prolonged (>1 month) episodes with more frequent immediate and long-term consequences of the disease, prompting therapeutic trials.

Kleine-Levin syndrome-like symptoms in a middle-aged female with cognitive dysfunction

Kleine-Levin syndrome is characterized by recurrent episodes of hypersomnia with cognitive and behavioral impairments. Two years ago, a 56-year-old female patient developed episodic memory loss and calculation difficulties. One year ago, she complained of recurrent hypersomnia with hyperphagia. Episodes developed 1–2 times per month and each episode lasted 3–4 days. Electroencephalography showed 6–7 Hz diffuse background slowing during an episode. Neuropsychological tests revealed cognitive impairment and brain imaging showed normal between episodes. Polysomnography showed increased periodic limb movement and respiratory disturbance index. This is the case of Kleine-Levin syndrome like symptoms in a patient with cognitive dysfunction.

A Case of Atypical Kleine-Levin Syndrome

Received December 8, 2013 Revised December 9, 2013 Accepted December 9, 2013 Address for correspondence Ho-Won Lee, MD, PhD Department of Neurology, School of Medicine, Brain Science & Engineering Institute, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842, Korea Tel: +82-53-200-3271 Fax: +82-53-200-3299 E-mail: neuromd@knu.ac.kr Kleine-Levin syndrome is characterized by recurrent episodes of hypersomnia and associated cognitive and behavioral impairments. We present a 47-year-old female patient with recurrent hypersomnia and disorder of appetite. During each episode, patient slept more than 24 hours with hyperphagia or anorexia. Physical examinations, laboratory tests, and brain MRI showed no significant abnormality in the patient. Nocturnal polysomnographic study showed high sleep efficiency, reduced sleep latency and rapid eye movement (REM) sleep latency, and increased sleep stage 1 & 2. The multiple sleep latency tests showed one episode of sleep-onset REM periods. This is the first atypical case report of Kleine-Levin syndrome in Korea which showed short duration of episodes and hypersomnia combined with anorexia. J Korean Sleep Res Soc 2013;10:56-58

1189 – Kleine-levin syndrome and lithium

Introduction Kleine-Levin syndrome (KLS) is a rare disease characterized by recurrent episodes of hypersomnia, hyperphagia and behavioural symptoms, mainly hypersexuality. Objectives We report the clinical course of KLS in a 18-year-old male. The clinical onset and evolution are described. Aims/methods The boy was diagnosed as having KLS after two episodes of hypersomnia lasting for 13 to 15 days each one. When awake, he was depressed and with megaphagia. He also had phases of hypersexuality. The initial interval between episodes was 6 weeks. After the second episode was treated with lithium and remained free of symptoms for 11 months. He had a third episode that lasted 6 days. Serum lithium level was low. In this third episode he had only hypersomnia. He had a relapse two years later with a duration of 4 days, without further relapses. Results KLS is more frequent in young males with a mean duration of 8 years and around 7 episodes that lasted 10 days. The pathogenesis remains unknown. It has been related with functional disturbance in the hypothalamus, viral infections, triggering stimulus...Some authors consider KLS as a variant of bipolar disorder. Treatment includes methylphenidate, neuroleptics, antidepressants and mood stabilizers as lithium. With lithium has been reported fewer relapses, shorter duration of episodes and disappearance of behavioural symptoms. Conclusions Despite being a rare disease, is thought to be underdiagnosed, because diagnosis is mainly clinical, and tests such as EEG, PSG and MSLT reinforce the diagnosis but are not pathognomonic. Today, lithium is the best treatment option.

Effects of various drug therapies on Kleine–Levin syndrome: a case report

Kleine–Levin syndrome (KLS) is a rare sleep disorder, predominantly affecting adolescent males, which presents as recurrent episodes of hypersomnia, behavioral and cognitive disturbances, hyperphagia and sometimes hypersexuality (Lisk, “Kleine–Levin syndrome.” Pract Neurol 2009;9:42–45). Modafinil has been reported to show an effect in shortening the duration of symptomatic periods, but does not affect the recurrence rate (Huang et al., “Kleine–Levin syndrome: current status.” Med Clin N Am 2010;94:557–562). However, no single drug therapy has been consistently successful, despite various psychotropic agents, including lithium, anticonvulsants and antidepressants, having been systematically tried (Arnulf et al., “Kleine–Levin syndrome: a systematic study of 108 patients.” Ann Neurol 2008;63:482–492). This study reports a male adolescent with KLS who received several courses of drug therapy, providing a chance to compare differential drug effects over time.

Distribution of HLA-DQB1 alleles in patients with Kleine-Levin syndrome

Kleine-Levin syndrome (KLS) is a rare disorder characterized by recurrent episodes of hypersomnia, cognitive or behavior disturbances, compulsive eating behavior, and hypersexuality. The etiology of KLS remains unknown even though its clinical symptoms suggest an underlying autoimmune process. In this study, we analyzed the human leukocyte antigen (HLA) typing alleles in Taiwanese patients with KLS using the polymerase chain reaction sequence-specific priming technique. We report that an immunoresponsive HLA-DQB1, DQB1∗0602, was detected in significant quantities in patients with KLS (three of 12, p=0.046) and could elevate the risk of KLS (odds ratio, 1.143; 95% confidence interval, 0.0982–1.329). In conclusion, an identification of genomic susceptibility to KLS will be helpful in determining the immunospecific targeted therapies for patients with KLS.

A case of PANDAS with Kleine–Levin type periodic hypersomnia

We report on an 11-year-old girl, presenting with clinical features suggesting both pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and Kleine-Levin syndrome (KLS), who was successfully treated with penicillin prophylaxis. KLS is a sleep disorder characterized by recurrent episodes of hypersomnia and at least one of the following symptoms: (1) cognitive or mood disturbances, (2) megaphagia with compulsive eating; (3) hypersexuality with inappropriate behaviors; and (4) abnormal behavior. The etiopathogenesis is still unclear and there is no effective treatment other than symptomatic therapies. This intriguing case report suggests novel insight into the pathogenesis of this rare and enigmatic syndrome.

Atypical Kleine–Levin syndrome: Can insomnia and anorexia be features too?

Background Kleine–Levin syndrome is an uncommon disorder with recurrent episodes of hypersomnia, clearly associated with behavioral abnormalities like binge eating, hypersexuality and abnormal behavior. Many patients may not necessarily fulfill minimum criteria described for diagnosis. We aim to report such patients with atypical presentation resembling the Kleine–Levin syndrome. Method We evaluated all patients at our clinic who had episodic disturbance in sleep and/or appetite lasting a few days to weeks, not necessarily fulfilling the International Classification of Sleep Disorders (ICSD) criteria for a diagnosis of Kleine–Levin syndrome, over 4 years. All clinical details, especially regarding sleep, appetite and behaviour during episodes, about prior and co-existing illnesses were noted. All patients were investigated with brain magnetic resonance imaging (MRI), electroencephalogram (EEG) and some with polysomnography. Results Eighteen patients (5 females, 13 males) ranging in age from 12 to 55 years (median 18 years) were included in the study. The median duration of symptoms was 1.5 years, and the median number of episodes in each patient was six. The range of episode length was 18–300 h with a mean of 91.2 h. Fourteen patients had a history of hypersomnia, 3 had only insomnia and 3 had both during their episodes, while 5 patients reported hyperphagia, 11 reduced appetite and 2 no change in appetite. Ictal EEG revealed evidence of sleep, while polysomnography showed reduced rapid eye movement (REM) latency and normal sleep architecture during the episode. MRI was normal in all patients, except one who showed non-specific abnormalities. All patients showed improvement with carbamazepine. Conclusion There are many patients with episodic alteration in sleep, appetite and behaviour with a course and treatment response similar to the classical Kleine–Levin syndrome, who otherwise do not fit the classical description for diagnosis of this condition.

Posttraumatic Kleine–Levin syndrome

Kleine–Levin Syndrome (KLS) is a rare disorder which most commonly occurs in adolescent males [1]. However, cases of KLS in females and older adults have been reported [2–4]. The key episodic triad of the syndrome are hypersomnia, hyperphagia and hypersexuality. The revised International Classification of Sleep Disorders (ICSD) provides the most comprehensive definition of KLS, which is classified as brecurrent hypersomniaQ [5]. It is characterised by recurrent episodes of hypersomnia, and the associated features during the episodes include at least one of the following: voracious eating, hypersexuality, disinhibited behaviours (such as irritability, aggression, disorientation, confusion and hallucinations), absence of urinary incontinence and presence of verbal responses to strong stimulation. Indiscriminate hypersexuality including inappropriate sexual advances and overt masturbation can be seen in males (and less often in females) [6]. KLS is described under the brecurrent form of primary hypersomniaQ in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IVTR) [6]. However, in the International Classification of Diseases, Tenth Revision (ICD-10), it is classified as bother sleep disordersQ in the section bDiseases of the Nervous System,Q rather than in the section of bMental and Behavioural DisordersQ [7]. The underlying pathophysiology and etiology of KLS is unclear. The hypothalamus, frontal lobe, and medial temporal lobe have been proposed to be involved in the development of KLS [3,8–13]. Few cases of KLS associated with head injury have been reported in the literature [1,4,14–16]. In this report, a case of posttraumatic KLS in an older man with an abnormal magnetic resonance imaging (MRI) brain scan is described. Computed tomography (CT) and MRI brain scan results on other cases of posttraumatic

Episodic Diencephalic Hypoperfusion in Kleine-Levin Syndrome

A 22 year-old woman suffered from recurrent episodes of hypersomnia, apathy, and hyperphagia. The symptoms occurred 3 to 4 times per year, and each attack lasted 2 to 3 weeks. 99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed during symptomatic and asymptomatic periods. To localize brain regions with perfusion changes during symptomatic period, asymptomatic SPECT was subtracted from symptomatic SPECT. The subtracted SPECT showed significant hypoperfusion in the left hypothalamus, bilateral thalami, basal ganglia, bilateral medial and dorsolateral frontal regions, and left temporal lobe during the symptomatic period. These cerebral hypoperfusion areas support the diencephalic hypothesis and clinical symptoms of Kleine-Levin syndrome.