Kleine-Levin Syndrome Research Articles

PET Study of Microglial Activation in Kleine-Levin Syndrome.

Kleine-Levin syndrome (KLS) is a rare recurrent hypersomnolence disorder associated with cognitive and behavioral disturbances, of unknown origin, but inflammatory mechanisms could be involved. We aimed to explore in vivo microglia activation using [18F]DPA-714 PET imaging in patients with KLS compared with controls, and during symptomatic vs asymptomatic periods. Patients with KLS and controls underwent a standardized clinical evaluation and PET imaging, using a radiolabeled ligand specific to the 18 kDa translocator protein. Images were processed on the PMOD (peripheral module) interface using a standard uptake value (SUV). Five regions of interest (ROIs) were analyzed: hypothalamus, thalamus, frontal area, cerebellum, and whole brain. SUV ratios (SUVr) were calculated by normalizing SUV with cerebellum uptake. Images of 17 consecutive patients with KLS (7 during episodes, 10 out of episodes) and 14 controls were analyzed. We found no SUV/SUVr difference between KLS and controls, between patients in and out episodes in all ROIs, and no correlation between SUVr and episode duration at the time of PET scan. No association was found between SUVr and sex, disease duration, or orexin levels. Our findings do not support the presence of neuroinflammation in KLS. Further research is needed to identify relevant biomarkers in KLS.

Kleine Levin syndrome - presentation of five cases.

Kleine Levin syndrome (KLS) is a rare entity. It presents with subacute onset episodic hypersomnia, cognitive decline, altered perception, and occasional hyperphagia and hypersexuality with full recovery during the interepisodic period. Five cases presented with episodic hypersomnia and met the diagnostic criteria of KLS. The majority of the cases were females (3/5) in whom KLS is even rarer. The initial presentation was in the age range of 10-25 years. Cognitive dysfunction (5/5), derealization (4/5), viral prodrome (3/5), hyperphagia (3/5), and hypersexuality (2/5) were other clinical presentations. A differential diagnosis of atypical depression is the major challenge, and thorough history taking would help in differentiation. Treatment with stimulants (modafinil) and mood stabilizers (lithium) proved effective. A high degree of suspicion should be kept for cases of episodic hypersomnolence for early diagnosis and management of KLS.

Back to the future: May Kleine-Levin syndrome be an emerging psychiatric disorder?

Back to the future: May Kleine-Levin syndrome be an emerging psychiatric disorder?

1201 A Drowsy Deployment Dilemma: Case Report of a Military Deployment-Induced Kleine-Levin Syndrome Episode

1201 A Drowsy Deployment Dilemma: Case Report of a Military Deployment-Induced Kleine-Levin Syndrome Episode

0656 Severe Air Pollution as a Possible Triggering Factor for Kleine-levin Syndrome

0656 Severe Air Pollution as a Possible Triggering Factor for Kleine-levin Syndrome

Kleine-Levin Syndrome in a Closed Psychiatric Ward: A Case of Misdiagnosis.

Kleine-Levin Syndrome in a Closed Psychiatric Ward: A Case of Misdiagnosis.

Kleine-Levin syndrome and bipolar affective disorder: a case report

Kleine-Levin syndrome and bipolar affective disorder: a case report

Atypical Kleine Levin Syndrome: Atypical or “Something Else”

Objective: To describe in some detail published cases who were diagnosed as atypical Kleine-Levin syndrome (KLS), and discuss the validity and usefulness of this diagnostic term. Methods: The English written literature was reviewed using the search terms Atypical KLS, KLS mimic, KLS like and KLS variant. Only reports which provided complete clinical features were reviewed. The present diagnostic criteria of KLS were applied in each case and the reasons why each case was considered as atypical were outlined in a table form. The cases were grouped according to the primary etiologies which could explain the symptoms into infectious, autoimmune, cerebrovascular, head trauma, brain tumor and genetic metabolic disorders. Cases in whom we could not establish a definite diagnosis were coined “atypical “and a few which could not be assigned to a specific group were coined “miscellaneous”. Results: Fifty seven reports describing 60 “atypical“ cases were found. Out of those, 14 suffered from a variety of medical conditions which could explain the symptomology while in 19 cases a definite diagnosis could not reached. Five cases were coined as “miscellaneous” since we could not assign them to a specific group. Conclusion: The eponym “atypical” KLS, refers to patients in whom a variety of medical disorders were associated with sleep-wake disorder, however, it seems appropriate that in such cases the diagnosis should express the primary cause of the symptoms rather than suggesting that those cases are a variant of KLS.

Kleine-Levin syndrome

Kleine-Levin syndrome (KLS) is manifested by periodic hypersomnolence with an increased appetite and psychopathological symptoms (psychomotor agitation, hallucinations, hypersexuality). The duration of the attack ranges from several days to several weeks. A forced awakening can provoke severe aggressive behavior. The disease occurs for an unknown reason, mainly in adolescence and mostly affects males. Lack of awareness among doctors about the disease leads to an incorrect diagnosis, often of a psychopathological disorder. This article presents modern data on the causes, clinical symptoms, diagnostic methods of KLS and provides a case of a 18 year-old man, whose disease manifested at the age of 16 years.

B - 95 A Case Study of Suspected Klein-Levin Syndrome and Associated Anxiety.

Neuropsychological assessment of ethnoracially diverse patients can be challenging for various reasons, including limited normative data, differing worldviews, stigma, and mental health service utilization and access. This case study describes the use of a comprehensive neuropsychological assessment to assist with differential diagnosis and treatment recommendations. The patient was a 25-year-old Asian and White female who was referred to rule out attention deficit hyperactivity disorder (ADHD). Her history included homeschooling through 8th grade, uncommon sleep disturbances, seasonal allergies, and a diagnosis of major depressive disorder. Regarding sleep disturbance, she endorsed monthly episodes of sleeping for up to 12hours at a time, sometimes sleeping and waking on the floor or elsewhere not in her bedroom. She underwent a comprehensive neuropsychological evaluation. The patient's cognitive profile was generally intact, with relative cognitive inefficiencies in visuospatial/visuoconstructional abilities, working memory, and processing speed domains. She also endorsed clinically significant levels of anxiety. These findings, in conjunction with family history and sleep disturbance, raised concern for Klein-Levin Syndrome (KLS) and the impact of co-occurring anxiety. A sleep study, educational/vocational accommodations, psychotherapy, and follow up evaluation in one year were recommended. While sleep-wake disorders and ADHD can co-occur, sleep-wake disorders can be overlooked by mental health professionals, thus increasing the likelihood of misdiagnosis and potential for harm. Adding additional complexity, expressions of psychological distress vary cross-culturally. Taken together, neuropsychological training must include frameworks that attend to cultural and contextual factors. These cases may frequently be seen in the context of educational or vocational concern referrals.

Clinical Evaluation and Management of Narcolepsy in Children and Adolescents

While sleepiness is common among children, and particularly adolescents, profound sleepiness in the setting of apparently adequate sleep should prompt consideration of a central disorder of hypersomnolence. These disorders, which include narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, and others, are likely underrecognized in the pediatric population. Narcolepsy in particular should be of interest to child neurologists as the unique signs and symptoms of this disease often prompt evaluation in pediatric neurology clinics. While sleepiness may appear to be a straightforward complaint, its evaluation requires a nuanced approach. Cataplexy, a hallmark of narcolepsy, can be confused for other neurologic conditions, though understanding its various manifestations makes it readily identifiable. Clinicians should be aware of these symptoms, as delay in diagnosis and misdiagnosis are common in childhood narcolepsy. While treatment options have been limited in the past, many new therapeutic options have become available and can result in significant improvement in symptoms. Given the age at presentation, paroxysmal and chronic features, diagnostic modalities, and available treatment options, the field of child neurology is well equipped to see patients with narcolepsy. In this review, I will focus on the presentation, evaluation, and management of pediatric patients with narcolepsy.

Idiopathic Hypersomnia and Kleine–Levin Syndrome: Primary Disorders of Hypersomnolence Beyond Narcolepsy

Daytime sleepiness is common amongst children and adolescents. Inadequate sleep duration, inappropriate school start times, and the delay in sleep phase of adolescence may all contribute. Nocturnal sleep disruption due to sleep disorders such as obstructive sleep apnea or restless legs syndrome/periodic limb movement disorder may also lead to daytime sleepiness. Profound sleepiness however, when occurring in the setting of adequate sleep duration, is rare amongst children and adolescents and may prompt consideration of a central disorder of hypersomnolence (CDH). Narcolepsy is the archetypal and most studied form of CDH and a detailed review of the presentation, evaluation, treatment of narcolepsy is included separately in this edition of Seminars in Pediatric Neurology. In addition to narcolepsy, 2 other forms of primary CDH exist, idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS). Onset of IH and KLS occurs most frequently during the pediatric age range and presentation may include signs of encephalopathy in addition to hypersomnolence. As such, they are of particular relevance to pediatric neurology and associated fields. Unfortunately, when compared to narcolepsy little is known about IH and KLS, at both the physiologic and clinical level. This review will focus on the presentation, evaluation, and management of idiopathic hypersomnia and Kleine-Levin syndrome in the pediatric population.

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.

An intriguing case of episodic hypersomnolence- Kleine–Levin syndrome, a diagnosis often missed

ABSTRACT A sleep disorder is characterised by alteration in normal pattern of sleep enough to interfere with the normal functioning of an individual. Sleep disorders are broadly classified as primary sleep disorders such as dyssomnias, hypersomnia and parasomnias and secondary due to medical and mental disorders such as anxiety or substance abuse. We report the case of a 12-year-old boy who presented to us with episodic hypersomnolence, hyperphagia and behavioural abnormalities and was initially managed as epilepsy at another hospital. He was subsequently diagnosed as primary sleep disorder, Kleine–Levin syndrome. We also describe the diagnostic approach to such a case and the crucial role of functional brain imaging in it.

A Rare Case of Kleine–Levin Syndrome Following COVID-19

A wide variety of neuropsychiatric manifestations have been reported with COVID-19. We present a case of a 45-year-old man who developed significant hypersomnia and hypersexual thoughts following COVID-19 illness. Further evaluation did not reveal any other infection, structural brain disease, or stroke, leading us to consider Kleine–Levin syndrome as a diagnosis of exclusion. However, a confirmed diagnosis of this syndrome cannot be made on initial presentation, and its formal diagnosis requires recurrence of symptoms. Although relapses of this syndrome are known to be triggered by viral illnesses, no primary occurrences have been reported with COVID-19 to date.

Diagnostic dilemma of Kleine-Levin Syndrome Mimicking Bipolar Depression: Case Report and Five-Year Follow-up.

Diagnostic dilemma of Kleine-Levin Syndrome Mimicking Bipolar Depression: Case Report and Five-Year Follow-up.

Protocolo diagnóstico de la somnolencia diurna excesiva

Excessive daytime sleepiness (EDS) is a common symptom that indicates the inability to remain alert during the day, an irresistible need to sleep, spontaneous daytime sleep, or prolonged nighttime sleep. EDS is a cause of functional impairment in the school, work, social, or family sphere as well as traffic accidents and cardiovascular risk. Therefore, it must be identified and treated. The most common cause of EDS is sleep deprivation. Other causes are toxic, drug, psychiatric disorders (depression), medical problems (obesity, hypothyroidism), primary sleep disorders (obstructive sleep apneas), or central hypersomnias (type 1 and 2 narcolepsy, idiopathic hypersomnia, or Kleine-Levin syndrome). With a detailed case history, it can be verified whether there is a known and treatable cause, although performing a sleep study is usually necessary to confirm the diagnosis. This document proposes an algorithm for an evaluation in the clinic, indications for additional tests in a sleep laboratory, and the management of these disorders.

A rare case: sleeping beauty syndrome

A rare case: sleeping beauty syndrome

Kleine Levin Syndrome: Is it just a sleep disorder? A review of psychiatric features during symptomatic and asymptomatic periods

Kliene Levin syndrome (KLS) is a peculiar sleep disorder of youth, consisting of idiopathic periodic hypersomnia attacks associated with behavioral and sometimes psychiatric symptoms during an attack. With the growing awareness of the syndrome and a steep rise in published cases, it became evident that psychiatric abnormalities may be present before the onset of hypersomnic events, in between events and first appear following years after complete recovery. Those observations suggest that psychiatric morbidity may be part of the symptomatology of KLS. In the present paper the results of a systematic literature search of publications using the key words KLS with psychiatric features, Atypical KLS, KLS like, KLS mimic and sleeping beauty syndrome will be discussed, in attempt to support the view that KLS is indeed a neuropsychiatric disorder and not just a sleep disorder of youth. Moreover, the recognition that KLS might imitate psychosis and other psychiatric disorders in which periodic hypersomnia is present, may decrease the number of KLS patients in whom the correct diagnosis may be delayed or totally missed.

FLUORO-DOPA pattern in Kleine Levin syndrome

Kleine Levin syndrome (KLS) is a rare neurological disorder characterized by excessive sleep with or without associated symptoms such as hyperphagia, abnormal behavior, cognitive dysfunction. Symptoms are cyclical and usually affect adolescents. Onset of symptoms is usually rapid and may last for days or weeks. The exact cause of KLS is unknown though it shows features of affection of hypothalamus that controls sleep, appetite and body temperature. There have been reports of viral infections preceding KLS raising a possibility of autoimmune response. Presented here is a six years old patient who had features of KLS. The FDG PET CT scan revealed hypometabolism in the thalami quite characteristic of the entity. F-DOPA scan revealed physiologic expression of dopaminergic activity in the neostriatum. However, the over-expression of dopaminergic activity in the right basi-frontal cortex and medial temporal lobe was also noted. The nigrostriatal, mesocortical, mesolimbic, tuberomammillary pathways are known dopamine transmitters. This case report attempts to explain the reason for dopaminergic expression in these regions in KLS.