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Kleine-Levin Syndrome Or Periodic Somnolence and Megaphagia Syndrome —A Review

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Kleine-Levin Syndrome Or Periodic Somnolence and Megaphagia Syndrome —A Review JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 11, 2020 KLEINE-LEVIN SYNDROME OR PERIODIC SOMNOLENCE AND MEGAPHAGIA SYNDROME —A REVIEW PALLAVI SARAH ALEXANDER1, GAYATHRI S G2, ROSHNI P R3 1,2 Student, Pharm D PB, Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita VishwaVidyapeetham, Kochi, Kerala, India 3Assistant Professor, Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita VishwaVidyapeetham, Kochi, Kerala, India [email protected], [email protected], [email protected] Received: 14 March 2020 Revised and Accepted: 8 July 2020 ABSTRACT: Kleine-Levin Syndrome is a sleep disorder which is sporadic and it is characterized by periodic episodes of hypersomnia, cognitive impairment, utmost food craving and increased sexual desire. The definite cause has not been identified and no effective treatments are available even though a well-defined clinical feature is observed. Around 1–5 per million individuals were consistently overwhelmed, and it is noticed that most of the teenagers are the victims of this disorder. In Ashkenazi Jewish population, the prevalence is considerably greater. This article reviews about the clinical symptoms, medical investigations and examinations, differential diagnosis, management and limitations. Mostly supportive treatment preferred, though a few medications that are stimulants which include MODAFINIL can help to subside the clinical manifestations. KEYWORDS: Kleine-Levin Syndrome, intermittent hypersomnia, binge eating, increased libido I. INTRODUCTION Kleine-Levin Syndrome (KLS) or sleeping beauty syndrome is a sporadic disease. The symptoms which are embodied with Kleine-Levin Syndrome are emotional disturbances, binge eating, lascivious, intermittent hypersomnia, irascibility, hallucinations, belligerent, experiences a loss of recognition and sense of context, extreme hunger and increased libido. Approximately around 1-5 cases per million populations are reported globally1.In 1925 Kleine primarily introduced the condition naming Kleine-Levin Syndrome and in 1936 Levin elaborated it. In 1942 Critchley and Hoffman delineated further about the syndrome2. The diagnostic standards for Kleine-Levin Syndrome were revised by International Classification of Sleep Disorders (ISCD) in 1990. Kleine-Levin Syndrome was found to be differentiated into primary and secondary based on the intrinsic effect of neuropsychiatric manifestations and excessive daytime sleepiness3.Kleine-Levin Syndrome is a sporadic disease which is usually affected among 1-5 per million individuals. This syndrome is mostly seen within the age group of 13 and 19 years. Males are at a greater risk of acquiring this disease when compared to females4.The incidence of this disease was reported in western countries and most of the cases were reported from Israel, which concluded a genetic link of KLS with Jewish population. Literature studies suggest that in 5% of cases reported it revealed a family history thereby concluding a genetic inclination with the disease5. II. ETIOLOGY The aetiology of Kleine Levin syndrome is not known. However, no scientific hypothalamic dysfunction has been reported6. The examination of the cerebrospinal fluid (CSF), imaging of the structural brain and the serum inflammatory markers were not remarkable7. Recently in Taiwanese patients it was found that there is an important correlation between Kleine-Levin events and prior upper respiratory tract infection (URI)8. Few cases were reported regarding the abnormalities in dopamine and serotonin levels, which indicated an imbalance in either serotogenic or dopinergic pathway9. III. CLINICAL PRESENTATION The signs and symptoms were described by the frequency of occurrence of the disease. HYPERSOMNIA Hypersomnia is a condition in which patient may experience excessive day time sleep from 12 to 21 hours. This symptom is very important for the diagnosis of Kleine Levin syndrome. The patients with Kleine Levin Syndrome know when an episode starts and ends because of the change in their symptoms. After the episode, patient may suffer from insomnia and then leads a normal life until the next episode begins. Kleine Levin Syndrome symptoms may be different in males and females but the idiopathic hypersomnia will be same for both sexes. Duration of 3453 JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 11, 2020 symptoms ranges from few days to a year10. In Kleine Levin Syndrome patients dissimilar polysomnography results are obtained in and out of the episode. An exceptional form of recurrent hypersomnia was observed with Menstruation related hypersomnia. This can be an alternative of Kleine Levin Syndrome. Menstruation related hypersomnia patients experience a lesser degree of cognitive impairment when compared with Kleine Levin Syndrome patients11. EATING BEHAVIOR DISORDER Excessive food cravings and polyphagia are the classic elements seen in Kleine Levin Syndrome cases. During the episodes most of patients had altered eating habits. Patients usually consume large amount of food, around 7-8 meals per day and have significant weight gain. Increased fluid intake was also reported in some cases12. MOOD DISORDERS AND INSTABILITY The patients with suicidal thoughts were about 15% and two suicidal cases were also reported. The depressed mood of the patients usually resolves at end of each episode and rarely does it persist for longer duration13. Around 8% of cases were disclosed to be hypomania for a span of two days at the end of Kleine Levin Syndrome episodes. Almost all the patients were presented with irritability peculiarly when sleep, sex or food drive was restricted. All these aberrancies were short lived and irreversible after each episode14. COGNITIVE DISTURBANCES Relatively all the cases with Kleine Levin Syndrome exhibited problems with communication, reasoning ability and working memory. Most of patients have partial or retrograde amnesia during episodes.Long term cognitive deficits which affect their speed of processing and verbal retrieving are also noted in some patients. Around 37% of patients have immediate episodic verbal memory15.In two third of the cases, abnormal speech was reported. The speech is usually short sentences, mute and slow in nature. Temporal disorientation occurs more frequent than spatial disorientation16. OTHER COMPULSIVE BEHAVIORS AND HYPERSEXUALITY During these episodes, closely half of the patients’ exhibit symptoms expressed with hyper sexuality which is significantly seen moreover in males than females. The symptoms seen in males such as exposing oneself, fonding gentitalia, increased or overt masturbation, making unwanted sexual advances and usage of pornographic language. Unwanted sexual advances may include molesting of female nursing staff, patient’s sister, female visitors, daughter or other female relatives17. Other compulsive behaviours were found to be common. One third of the patients will tend to repeat stride, sing, tap their fingers, listen to the same music or watch the same video. Inappropriate and irresistible singing, chewing lips, compulsive writing on walls, compulsion to set fire, body rocking, and stripping down wallpaper were the other compulsions which occurs during the episodes18. DEREALIZATION, HALLUCINATION AND DELUSION. Majority of patients experience a distorted or unreal altered perception during episodes. Patients are always in a dreamy state, totally or partially detached from environment. Some patients may show symptoms like both visual and auditory hallucinations. Some people visualize distorted faces, dead bodies of parents19. IV. MEDICAL INVESTIGATIONS AND EXAMINATIONS Neurophysiological and neurochemical abnormalities In Kleine Levin Syndrome examination of biochemical abnormalities has been unrewarding. There is a decreased production of hypocretin (orexin) in patients with Klein Levin Syndrome. Analysis of Cerebrospinal fluid orexin levels should be studied with care in Kleine Levin Syndrome patients, inorder to recognise the modest episodic reductions, which may not be evident in narcolepsy-cataplexy20. Recent research studies reported that there are significant changes in the catecholamine levels. Occasionally Klein Levin Syndrome patients showed an abnormal serotonin, serotonin metabolite, dopamine or nor epinephrine activity. Thus, the biochemical and neurophysiological studies excluding epileptiform activity and low orexin production may be observed as a cause of Kleine Levin Syndrome21. Polysomnography and Electroencephalography A normal EEG has been observed during episodes on one fourth of the patients. Mostly around 70% of cases have a background of vague diffuse that slowdown the EEG activity, such as alpha frequency band being gradual towards 7-8 HZ. In Klein Levin Syndrome patient brain Computerized Tomography and Magnetic Resonance Imaging is normal22. 3454 JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 11, 2020 Cerebrospinal Fluid Analysis Usually, in Kleine Levin Syndrome patients the serological inflammatory markers were found to be within the normal range. Serum and cerebrospinal fluid analysis shows no abnormalities in Kleine Levin Syndrome patients. In four patients, the cerebrospinal fluid analysis reveal that the cerebrospinal fluid levels of hypocretin-1 a hypothalamic peptide were found to be deficient in narcolepsy, where as in Kleine Levin Syndrome patients it was found to be normal23. Till date, there is no scientific evidence of cerebrospinal fluid hypocretin, to prove its significance
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