KLS Support UK - Helping families affected by Kleine-Levin Syndrome

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Medical Papers/Articles

Where only an abstract is available purchase may be necessary for full details; some abstracts do provide a lot of information.

2016

Migraine with brainstem aura presenting as recurrent hypersomnia (Kleine-Levin syndrome).

Pract Neurol. 2016 Jun 24. pii: practneurol-2016-001418. doi: 10.1136/practneurol-2016-001418.

Abstract here

Nesbitt AD, Leschziner GD.

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

Chin Med J (Engl). 2016 Jul 5;129(13):1565-8. doi: 10.4103/0366-6999.184476.

Abstract here

Luo YW, Yu H, Yuan LH, Zhu GX.

Familial Kleine-Levin Syndrome: A Specific Entity?

Sleep. 2016 May 25. pii: sp-00113-16. [Epub ahead of print]

Nguyen QT, Groos E, Leclair-Visonneau L, Monaca-Charley C, Rico T, Farber N, Mignot E, Arnulf I.

Abstract here

Prevalence and Mimics of Kleine-Levin Syndrome: A Survey in French-Speaking Switzerland.

J Clin Sleep Med. 2016 May 25. pii: jc-00018-16. [Epub ahead of print]

Habra O, Heinzer R, Haba-Rubio J, Rossetti AO.

Abstract here

New hypothesis on pontine-frontal eye field connectivity in Kleine-Levin syndrome.

J Sleep Res. 2016 May 27. doi: 10.1111/jsr.12428. [Epub ahead of print]

Engström M, Landtblom AM, Karlsson T.

Abstract here

Pharmacological treatment for Kleine-Levin syndrome.

Cochrane Database Syst Rev. 2016 May 6;(5):CD006685. doi: 10.1002/14651858.CD006685.pub4.

de Oliveira MM1, Conti C, Prado GF.

Full text available here

Kleine-Levin Syndrome.

Curr Neurol Neurosci Rep. 2016 Jun;16(6):60. doi: 10.1007/s11910-016-0653-6.

Miglis MG, Guilleminault C.

Abstract here

Kleine-Levin Syndrome.

Curr Treat Options Neurol. 2016 Jun;18(6):24. doi: 10.1007/s11940-016-0409-2.

Sum-Ping O, Guilleminault C.

Abstract here

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).

Case Rep Neurol Med. 2016;2016:8929413.

Assi B, Yapo-Ehounoud C, Baby MB, Aka-Diarra E, Amon-Tanoh M, Tanoh C.

Abstract here

Cerebrospinal Fluid Orexin A Levels and Autonomic Function in Kleine-Levin Syndrome.

Sleep. 2016 Jan 15. pii: sp-00389-15. [Epub ahead of print]

Wang JY, Han F, Dong SX, Li J, An P, Zhang XZ, Chang Y, Zhao L, Zhang XL, Liu YN, Yan H, Li QH, Hu Y, Lv CJ, Gao ZC, Strohl KP.

Abstract here

Kleine-Levin Syndrome: An Overview and Relevance to Nursing Practice

J Psychosoc Nurs Ment Health Serv. 2016 Mar 1;54(3):41-7

Arnone JM, Conti RP.

Abstract here

Differential Diagnosis of Kleine-Levin Syndrome

Pediatr Neurol Briefs. 2015 Mar;29(3):24

Millichap JG.

Abstract here

Kleine-Levin syndrome. Familial cases and comparison with sporadic cases

Saudi Med J. 2016 Jan;37(1):21-8

Al Suwayri SM.

Abstract here

Successful Use of Valproate in Kleine-Levin Syndrome: A Case Report and Review of Cases Reported from India

Indian J Psychol Med. 2015 Jul-Sep;37(3):352-4

Nebhinani N, Avasthi A, Modi M.

Abstract here

Kleine-Levin syndrome with comorbid iron deficiency anemia

Oxf Med Case Reports. 2015 Mar 10;2015(3):226-8.

Jain RS, Kumar S, Srivastava T, Sannegowda RB.

Abstract here

Do the Symptoms of Kleine-Levin Syndrome Correlate With the Hypometabolism of the Thalamus on FDG PET?

Clin Nucl Med. 2016 Mar;41(3):255-6

Xie H, Guo J, Liu H, Song W.

Abstract here

2015

Recurrent hypersomnia: Report of medication-responsive cases.

DOI: 10.1016/j.slsci.2015.06.003

Perin BV, Rodrigues I, Giasson FT, Balen M, Posenato N, Forcelini CM.

Abstract here

Lithium therapy in Kleine-Levin syndrome: An open-label, controlled study in 130 patients.

DOI: 10.1212/WNL.0000000000002104

Leu-Semenescu S, Le Corvec T, Groos E, Lavault S, Golmard JL, Arnulf I.

Abstract here

Kleine–Levin syndrome in 120 patients: Differential diagnosis and long episodes

DOI: 10.1002/ana.24350

Sophie Lavault, Jean-Louis Golmard MD,PhD, Elisabeth Groos MD, Agnès Brion MD, Yves Dauvilliers MD,PhD, Michel Lecendreux MD, Patricia Franco MD, PhD, Isabelle Arnulf MD, PhD.

Abstract here

Differential Diagnosis of Kleine-Levin Syndrome - PEDIATRIC NEUROLOGY BRIEFS March 2015

J. Gordon Millichap, MD

Download a pdf from the link here.

An unusual occurrence of Kleine-Levin syndrome in a man with refractory immune thrombocytopenic purpura:

a case report.

doi:10.1186/s13256-015-0536-5

Hamed Amirifard1, Farzaneh Barzkar, Seyed Amirhossein Fazeli and Seyed Mahdi Hashemi.

Abstract (provisional)

Conclusions Immune thrombocytopenic purpura may be associated with meningococcal vaccination in adulthood. Responses to treatment in immune thrombocytopenic purpura vary among patients. Our patient only had a transient acceptable response to intravenous immunoglobulin while all other options failed to improve his platelet count. Concurrence of immune thrombocytopenic purpura and Kleine-Levin syndrome supports the role of autoimmunity as the proposed pathophysiological mechanism of Kleine-Levin syndrome.

Full pdf (provisional) here

Kleine–Levin Syndrome: Sleeping Beauty: A Rare Case Report on Sleep Disorder.

Ajaykumar Dhage, Rahul Mandaknalli

Assistant Professor, Department of Psychiatry, M.R. Medical College, Gulbarga, Karnataka, India
Int J Sci Stud 2015;2(11):209-210.
pdf here

CONCLUSION
This case report aim to highlight that KLS though
considered a rare disorder but not uncommon and lack of
enough available research data is likely to be responsible
for missed or erroneous diagnosis; thus we require more
systematic studies regarding etiologies and treatment.

Pharmacological treatment for Kleine-Levin syndrome

Marcio M Oliveira1, Cristiane Conti1, Gilmar F Prado.

DOI: 10.1002/14651858.CD006685.pub3
NOW ONLINE

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 2, 2009) on 'Pharmacological treatment for Kleine-Levin syndrome'.

Authors' conclusions
Implications for practice
No evidence indicates that pharmacological treatment for Kleine-Levin syndrome is effective and safe.

Abstract here

Preliminary results on CSF biomarkers for hypothalamic dysfunction in Kleine-Levin syndrome.

Lopez, Barateau, Chenini, Dauvilliers.

Sleep Med. 2015 Jan;16(1):194-6. doi: 10.1016/j.sleep.2014.07.022. Epub 2014 Oct 22.
Abstract here

More information is available from Hypersomnia Foundation here

The results of this study indicate that hypocretin levels in the CSF appeared to correlate with KLS episodes in these two patients and may, therefore, serve as a biomarker of KLS. However, additional larger studies are needed to support this finding.

Recurrent hypersomnia

Contributors

Rosalia C Silvestri MD, author. Dr. Silvestri, Director of the Interdepartmental Sleep Center at the University of Messina, has no relevant financial relationships to disclose.

Antonio Culebras MD, editor. Dr. Culebras of SUNY Upstate Medical University has no relevant financial relationships to disclose.

Publication dates
Originally released October 11, 1993; last updated June 19, 2014; expires June 19, 2017
Spotlight on Recurrent hypersomnia
Posted on January 26, 2015

Spotlight on Recurrent hypersomnia
Although rarely observed, Kleine-Levin syndrome is an interesting disorder affecting 1 to 2 patients per million inhabitants worldwide and is associated with recurrent cognitive behavioral and emotional problems. It may severely affect quality of life and social adaptation. Increasing evidence points to a diencephalic dysregulation as the main source of symptoms. Recent functional neuroimaging results, as well as late reports of 2 affected couples of monozygotic twins, provide new insights to better understanding of the physiopathology of this disorder. Clinical and cognitive follow-up of affected patients has in several cases demonstrated persistence of memory impairments long after resolution of episodes of the disorder itself, especially in patients with longstanding disease. A recent Cochrane review of drug trials for the management of Kleine-Levin syndrome symptoms did not find eligible studies to recommend any of the different treatments so far employed, even if therapeutic. Lithium seems to hold the best prospective benefits.

Clinical Summary Link here

2014

Kleine-Levin Syndrome: Diagnosing, Symptoms, Causes and Treatment

Thomas C. Weiss

Disabled World, Health and Disability, Neurological Disorders. 17 December 2014
Link to article

SPECT in the Kleine–Levin syndrome, a possible diagnostic and prognostic aid?

Patrick Vigren1, Maria Engström, Anne-Marie Landtblom.

Front. Neurol., 23 September 2014

Original research article here

Thalamic Activation in the Kleine-Levin Syndrome

Maria Engström, PhD1,; Thomas Karlsson, PhD2,; Anne-Marie Landtblom, PhD, MD2.

1Department of Medical and Health Sciences (IMH), Division of Radiology, Linköping University, Linköping, Sweden; 2Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; 3Department of Behavioral Science and Learning, Division of Disability Research and Linnaeus Centre HEAD, Linköping University, Linköping, Sweden; 4Department of Clinical and Experimental Medicine (IKE), Division of Neurology, Linköping University, UHL, LiM, Linköping, Sweden
VOLUME 37, ISSUE 02 of Sleep

Link to full article here
Good summary here

A striking response to lithium in Kleine–Levin syndrome

Olafur Sveinsson, Department of Neurology, Karolinska University Hospital, Stockholm, Sweden

CLINICAL CASE STUDY ARTICLE Front. Neurol., 21 March 2014 | doi: 10.3389/fneur.2014.00033

Link to article here

Psychosis in a case of Kleine-Levin syndrome: A diagnostic challenge

Vasantmeghna Srinivasa Murthy, Amol Deepak Kelkar, Sushma Sanjiv Sonavane

Department of Psychiatry, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, Maharashtra, India
Date of Web Publication 17-Apr-2014

Link to abstract here

Functional magnetic resonance imaging in narcolepsy and the Kleine–Levin syndrome

Maria Engström1,Tove Hallböök, Attila Szakacs, Thomas Karlsson, Anne-Marie Landtblom.

25 June 2014.

Link to full article here

Recurrent encephalopathy? No I'm a sleeping beauty!

Mehtab Iqbal, Manish Prasad, Christopher Ritey

Department of Neurology, Sheffield Children's Hospital, Sheffield, South Yorkshire, United Kingdom. Published on Web 25 April 2014

To describe the clinical presentation of 'Kleine-Levin (sleeping beauty) syndrome' in a child, who presented with recurrent episodes consistent with encephalopathy, associated with excessive sleepiness, cognitive and behavioural disturbance and hyper sexuality. 14 years old boy presented acutely with excessive tiredness, sleeping excessively, abnormal behaviour and hypersexuality following a viral throat infection. On examination he was sleepy but easily arousable. His GCS (15/15) and rest of the neurological exami...

Source: Journal of Pediatric Neurosciences - April 25, 2014 Category: Neuroscience

Link to abstract here

Kleine-Levin Syndrome with Rapid Cycling - Case Report and Review of the Literature (P5.294)

Claudio De Gusmao, Kiran Maski1 and David Urion.

CONCLUSIONS: KLS has significant morbidity if unrecognized. We review and discuss updated diagnostic criteria, pathophysiology and management. This case exemplifies an unusual rapid cycling pattern of hypersomnia episodes associated with classic KLS symptoms.

Source: Neurology - April 9, 2014 Category: Neurology

Link to abstract here
© 2014 American Academy of Neurology.

Widespread hypermetabolism in symptomatic and asymptomatic episodes in Kleine-Levin syndrome

Dauvilliers, Bayard, Lopez, Comte, Zanca, Peigneux. 2014 Apr 3

Abstract here

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

Sleep and Biological Rhythms, 05/20/2014 Clinical Article

Summary only here

Reduced thalamic and pontine connectivity in Kleine–Levin syndrome

Maria Engström1, Thomas Karlsson and Anne-Marie Landtblom

CLINICAL CASE STUDY ARTICLE Front. Neurol., 02 April 2014 | doi: 10.3389/fneur.2014.00042

Concluding Remarks
This case study of one KLS patient, for whom results were possible to obtain during both hypersomnic and asymptomatic periods, suggests that KLS might be associated with disrupted thalamo-pontine functional connectivity.
The results also indicate that neuropathology in the dorsal pons might be a common factor behind both the patient’s nystagmus and her hypersomnia.

A pdf of the article is available here

Feeling unreal: a functional imaging study in patients with Kleine-Levin syndrome

Aurelie Kas, Sophie Lavault, Marie-Odile Habert and Isabelle Arnulf.

PDF here
Published in Brain, A Journal of Neurology. doi:10.1093/brain/awu112 Brain 2014: 137; 2077–2087 |

Kleine-Levin syndrome: a review

Mitchell G Miglis & Christian Guilleminault

Available from Dove Press Open Access Peer-Reviewed BioMedical and Scientific Journals here

2013

The Kleine-Levin syndrome: new aspects of a rare disease

Mayer G

Nervenarzt. 2013 Oct;84(10):1207-12. doi: 10.1007/s00115-013-3858-9.
Abstract here
Link to the original German version here

Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome

Patrick Vigren equal contributor mail, Anders Tisell equal contributor, Maria Engström, Thomas Karlsson, Olof Leinhard Dahlqvist, Peter Lundberg, Anne-Marie Landtblom

Published: February 25, 2013
Research article link here

Pharmacological treatment for Kleine-Levin syndrome

Oliveira MM1, Conti C, Prado GF.

CONCLUSIONS: Therapeutic trials of pharmacological treatment for Kleine-Levin syndrome with a double-blind, placebo-controlled design are needed.

Abstract here

Kleine-Levin Syndrome Treated With Clarithromycin

Elham Rezvanian, M.D.1,2; Nathaniel F. Watson, M.D., M.Sc., F.A.A.S.M.1,3

Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by periodic hypersomnia and various degrees of cognitive and behavioral disturbance, hyperphagia, and hypersexuality. Effective treatment is challenging. Stimulants marginally address sleepiness, but may increase irritability and do not improve cognitive and behavioral disturbances. Modafinil may shorten the symptomatic period but not the recurrence rate. Lithium and carbamazepine are beneficial in some cases, possibly related to similarities between KLS and affective disorders. Currently, no single medication is consistently successful in treating the syndrome. Here we report the short-term effect of clarithromycin in a patient with KLS.

Abstract here

Short-term memory dysfunction in Kleine-Levin syndrome

Landtblom A-M, Dige N, Schwerdt K, Säfström P, Granérus G.

Acta Neurol Scand 2003: 108: 363-367. © Blackwell Munksgaard 2003.
Link to pdf here

2012

A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes

Emmanuel J. M. Mignot

Available to download here

Diagnosis, disease course, and management of patients with Kleine-Levin syndrome

Prof Isabelle Arnulf, MDa, Thomas J Rico, BSb, Prof Emmanuel Mignot, PhDb.

Summary only here. This is available to purchase.

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

Huang CJ, Liao HT, Yeh GC, Hung KL.

Abstract only here

Monozygotic twins concordant for Kleine-Levin syndrome

Taro Ueno, Akira Fukuhara, Azusa Ikegami, Fumihiro Ohishi and Kazuhiko Kume, 30 May 2012

© 2012 Ueno et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Case report here

A case of PANDAS with Kleine-Levin type periodic hypersomnia

Das A, Radhakrishnan A.

Abstract only here

Relationship between Kleine-Levin syndrome and upper respiratory infection in Taiwan

Huang YS, Guilleminault C, Lin KL, Hwang FM, Liu FY, Kung YP.

Abstract only here

Kleine Levin syndrome in Malaysia: first typical case

Bahari R, Ahmad SH

Abstract only here

Earlier articles

Gupta R, Lahan V, Srivastava M. Kleine-Levin syndrome and idiopathic hypersomnia: Spectrum disorders. Indian J Psychol Med 2011;33:194-8

Abstract here

(1 Feb 2011) Kleine-Levin syndrome: A Case Report from Iran

Reza Bidaki, MD•, Mahsa Sedaghati, MS, Mitra Hakim-Shooshtari, MD* , Mir Farhad Ghalebandi, MD**

Abstract only here

RECURRENT HYPERSOMNIAS : A REVIEW OF 339 CASES

Michel Billiard, Isabelle Jaussent, Yves Dauvilliers, Alain Besset

Department of Neurology, Gui de Chauliac Hospital, Montpellier, France
INSERM U888, University of Montpellier I, Montpellier, France
National Reference Network for Orphan Diseases (narcolepsy, idiopathic hypersomnia and
Kleine-Levin syndrome, Gui de Chauliac Hospital, Montpellier, France

Link to pdf here

(2010) Kleine-Levin syndrome: current status

Huang YS, Lakkis C, Guilleminault C.

Abstract only here

(2010) Kleine–Levin syndrome: Etiology, diagnosis, and treatment

Santosh Ramdurg - Copyright © Annals of Indian Academy of Neurology

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 here

(2010) Recurrent hypersomnia: a review of 339 cases

Billiard M, Jaussent I, Dauvilliers Y, Besset A.

Abstract only here

(2009) Working memory in 8 Kleine-Levin syndrome patients: an fMRI study

Engström M, Vigren P, Karlsson T, Landtblom AM.

Abstract only here

Combining fMRI with qMRS for understanding the etiology of periodic hypersomnia

A. Tisell, M. Engström, O. D. Leinhard, T. Karlsson, P. Vigren, A. Landtblom, and P. Lundberg.

Conclusion
The strong correlation between NAA concentration and fMRI activation during the working memory test indicates a damage of the thalamus in the patient group. Increased mIns are a sign of phospholipids break down which can be interpret as membrane damage, analogous with demyelization in MS [8].

PDF link here

(2008) Kleine-Levin syndrome: a systematic study of 108 patients

Arnulf I, Lin L, Gadoth N, File J, Lecendreux M, Franco P, Zeitzer J, Lo B, Faraco JH, Mignot E.

Abstract only here

Polysomnography in Kleine-Levin syndrome

Yu-Shu Huang, MD, Yu-Hsuan Lin, MD and Christian Guilleminault, MD, BiolD

Conclusion: Important changes in sleep occur over time during the symptomatic period, with clear impairment of slow wave sleep at symptom onset. But Multiple Sleep Latency Test (MSLT) is of little help in defining sleep problems and findings from the MSLT do not correlate with symptom onset.

Abstract here

(2008) Kleine-Levin syndrome: state of the art

by Arnulf I, Lecendreux M, Franco P, Dauvilliers Y.

Centre de référence maladies rares : narcolepsie, hypersomnie et syndrome de Kleine-Levin, France.
isabelle.arnulf@psl.ap-hop-paris.fr
Rev Neurol (Paris). 2008 Aug-Sep;164(8-9):658-68.
Modafinil Link here
Article Link from Orphanet here

(2007) Kleine-Levin syndrome: interface between neurology and psychiatry

Luís Pereira Justo; Helena Maria Calil; Sílvia A. Prado-Bolognani; Mauro Muszkat.

Link here

(2006) Kleine-Levin syndrome in a 14-year-old girl: CSF hypocretin-1 measurements. Sleep Med.

Podestá, Ferreras M, Mozzi M, Bassetti C, Dauvilliers Y, Billiard M.

Abstract here

(2005) SPECT Findings in the Kleine-Levin Syndrome

Yu-Shu Huang, MD1,2,4; Christian Guilleminault, MD, BiolD4; Pan-Fu Kao, MD3; Feng-Yuan Liu, MD3

Abstract with a PDF/Print button too here

(2005) Kleine–Levin syndrome: a systematic review of 186 cases in the literature

Arnulf, J M Zeitzer, J. File, N. Farber and E. Mignot

Whole article here

(2004) Kleine-Levin syndrome: a unique cause of fatigue in an athlete

C M J Conklin1, J E Taunton1

Full text here

(2003) The Kleine-Levin syndrome - effects of treatment with lithium -

Poppe M, Friebel D, Reuner U, Todt H, Koch R, Heubner G.

Abstract here

(2003) Working Memory in 8 Kleine-Levin Syndrome Patients: An fMRI Study

Maria Engström, PhD1,2; Patrick Vigren, MD3; Thomas Karlsson, PhD4; Anne-Marie Landtblom, MD, PhD2,3

Abstract with a PDF/Print button too here

(2002) Familial Kleine-Levin Syndrome -Two Siblings With Unusually Long Hypersomnic Spells

Joshua D. Katz, MD; Allan H. Ropper, MD

Abstract here

(1998) KLEINE-LEVIN SYNDROME CLINICAL COURSE, POLYSOMNOGRAPHY AND MULTIPLE SLEEP LATENCY TEST

Case Report

RUBENS REIMÃO, MARISA H. SHIMIZU

Abstract only here

(1996) Bhatia MS, Choudhary S. Kleine - levin syndrome - A case report with a brief review

Indian J Med Sci 1996;50:342-4
Brief review here

(1994) The Kleine-Levin syndrome: Clinical and quantitative electroencephalographic findings in two patients

Winterer, Georg; Bes, F.; Ziller, M.; Herrmann, W. M.,

Abstract here.

Observation of a nervous disease attended by disturbed sleep, at times lethargic and at times convulsive

Edmé Chauvot de Beauchêne (1786)

Beauchêne offers the oldest observation currently identified which is consistent with KLS.
Full text here
book image

Sections in Books

Psychiatry and pediatrics Chapter I.4

Sleep disorders in children and adolescents a practical guide

Samuele Cortese, Anna Ivanenko, Ujjwal Ramtekkar & Marco Angriman

Pages 22/23 KLS including 2014 diagnostic critera.
This publication is intended for professionals training or practicing in mental health and not for the general public.

PDF link here

Sleepiness: Causes, Consequences and Treatment

By Michael J. Thorpy, Michel Billiard

chapter 13, Sleep Disorders and Excessive Sleepiness, Kleine-Levin Syndrome

This is an excerpt from the book, not all pages may be available to view.

Link here

image of newspapers

General Medical Articles in Newspapers etc.

Kleine-Levin Syndrome May Be Misdiagnosed as Bipolar Disorder

By Marcia Purse, Bipolar Disorder Expert

'abouthealth' article link here
Updated September 12, 2014.

Scientists Try to Unravel the Riddle of Too Much Sleep

The Wall Street Journal, Europe Edition, Monday, December 10, 2012

Link here